Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ionchannel and protein kinase, participating in a wide variety of diseases including cancer. Recent researcheshave reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 andprostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potentialthe role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In thisstudy, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis inducedby TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression ofTRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors(Gd3+ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, butalso increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleavedCaspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Takentogether, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced byTRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.