Density functional theory (DFT) calculations was used to investigate the interaction between the prefect and defected boron carbide (BC3) monolayer nanosheet and conventional acetaminophen (AP) drug. The obtained findings indicate no considerable interaction between BC3 nanosheet and AP drug. Thus, perfect BC3 is not highly sensitive against AP presence regarding weak interactions. We explored if introducing single vacancy (SV) and double vacancy (DV) defect in prefect BC3 nanosheet can enhance the interaction with AP drug. The adsorption energy of AP drug on the DV-BC3 and SV- BC3 surface were calculated about -15.32 and -23.78 kcal/mol, respectively. After AP adsorption, a considerable change of bang gap and work function of DV-BC3 and SV-BC3 was observed while only the electrical bang gap of perfect BC3 was changed after AP adsorption and the work function change was negligible. It can be concluded that both defected BC3 sheets can act as both electrical and work function sensor types while the perfect BC3 can only act as an electrical sensor. The adsorption energy is remarkably changed in media with higher dielectric constant. Additionally, AP adsorption dramatically changes the magnetic properties of DV-BC3.