T-cell acute lymphoblastic leukemia (T-ALL) is a violent hematologic malignancy that is happening because of the oncogenic conversion of immature T-cell progenitors and is generally represented via the penetration of the bone marrow by malignant lymphoblasts [1]. At the present time, T-ALL accounts for 20–25 percent of adults and 10–15 percent of ALL children [2, 3]. Currently, treatment of T-ALL includes high-intensity combination chemotherapy which leads to high survival in children [4]. Unfortunately, chemotherapy has short-term and long-term side effects particularly for young children, the effects of high-dose chemotherapy on the development of bones and the central nervous system should not be ignored [5, 6]. In addition to side effects, relapse is another important challenge that can be seen in 20% of children and 40% of T-ALL adults [7–9]. In recent years, many studies have been conducted to improve the effectiveness of anticancer agents. However, due to drug resistance, most patients especially advanced cancer patients, experience chemotherapy failure [10, 11]. Doxorubicin is a cytotoxic drug taken from mutated strains of Streptomyces. Doxorubicin is one of the strongest FDA chemotherapy drugs that offer great therapeutic potential and is an effective treatment for acute lymphoblastic leukemia (ALL) [12]. A study found that treatment with doxorubicin could induce G2 arrest, but essentially no apoptosis in the Jurkat cell line [13]. The discovery of miRNAs has created a new generation for understanding carcinogenesis, especially leukemogenesis [14, 15]. The emergence of miRNAs as gene expression regulators identifies them as emerging diagnostic and prognostic candidates and potential therapeutic targets [16]. The improper expression of miRNAs can act as an oncogene or tumor suppressor in T-ALL. MiRNAs show a pivotal role in the advancement of T-ALL by regulating cell migration, proliferation, and cell death, and chemotherapy resistance through targeting major signaling pathways or transcription factors [14]. Several studies have examined the expression of microRNAs in T-ALL. The results demonstrated that ten miRNAs were highly expressed, including miR-223, miR-19b, miR-20a, miR-92, miR-142-3p, miR-150, miR-93, miR-26a, miR-16, and miR-342. In addition, the analysis of 3′ UTRs of tumor suppressor genes indicated that five of these highly expressed miRNAs ranked highest in this analysis (miR-19b, miR-26a, miR-92, miR-20a / 93, and miR-223) [17]. In another study, Renou et al. evaluated the expression patterns of 738 miRNAs in pediatric T-ALLs using high-throughput real-time quantitative polymerase chain reaction (R-Q-PCR) analysis. They illustrated that the expression of two clustered miRNAs, miR-125b/99a, increased and reached the peaks in primitive T cells and was also upregulated in the T leukemia homeobox 3 (TLX3) subtype of T-ALL [18]. Moreover, in another study, Wallaert et al. indicated novel miRNAs with extremely high expression levels in various T-ALL patient samples using small RNA-sequencing: hsa-miR-181b-5p (acute myeloid leukemia (AML)), hsa-miR-423-3p, hsa-miR-486-5p (down syndrome myeloid leukemias), and hsa-miR-92b-3p (TLX1/3 T-ALL) [19]. Family members of the miR-34 include three processed miRs that are encoded by two distinct genes: miR-34a is encoded with its own transcript, whilst miR-34b and miR-34c share common transcripts [20]. MiR-34a is a tumor suppressor with reduced expression levels in many cancers [21]. MiR-34a inhibits tumor growth by inhibiting various cellular processes in cancer, including epithelial-to-mesenchymal transition (EMT), cell cycle, metastasis, and inducing apoptosis. MiR-34a regulates these processes by reducing the expression of target mRNAs [22]. In latest years, many experiments have been conducted on the combination of miRNA-based therapeutics and chemotherapy in the treatment of cancers [23]. MiR-34a has been analyzed in combination with various chemotherapy drugs to expand the apoptosis of tumor cells as well as to reduce tumor growth and proliferation [20]. A study by Chao and colleagues showed that the combination of Doxorubicin/Sorafenib or miRNA-34a synergistically suppresses the growth of 143B osteosarcoma cells [24]. In another study by Qing et al., MiR-34 mimic caused apoptosis and sensitivity of pancreatic cancer cells to Gemcitabine [25]. Moreover, a study by Marques et al., indicated that miR-34a overexpression increases response to doxorubicin in diffuse large B-cell lymphoma (DLBCL) [26]. According to the studies and their results as well as the analyzes performed, the Jurkat cell line was selected for this study. To date, no study has been conducted on the antitumor effect of the combination therapy with miR-34a and doxorubicin in T-ALL, Jurkat cell line. Therefore, in this study, we investigated the effect of the combination of doxorubicin and miR-34a on growth inhibition and induction of apoptosis on T-cell acute lymphoblastic leukemia (T-ALL), Jurkat cell line.