Physiological status can influence social behavior, which reciprocally can impinge on physiology and health. We previously reported that tumor growth in Drosophila virgin females depends on the social context. However, neither the underlying physiological mechanisms nor their extent to different physiological status have been investigated to date. Transcriptome analysis from the heads of these tumorous flies now reveals social-dependent gene-expression changes related to nervous-system activity, suggesting that a cognitive-like relay might mediate the tumor suppressive effect. Surprisingly, this social-dependent tumor-suppressive effect is lost in fertilized females. After mating, Drosophila females change their behavior to favor offspring survival in response to peptides transferred via the male ejaculate, a process called “male manipulation”. Remarkably, the social-dependent tumor suppressive effect is restored in females mated by sex-peptide deficient males. Since male manipulation has likely been selected to favor male gene transmission, our findings indicate that this evolutionary trait impedes social-dependent tumor growth slowdown.