Objective: This study investigated the effects of rh-TRAIL with or without chemotherapeutic drugs on the apoptosis of the osteosa-rcoma cell line, MG-63, and the influence of chemotherapeutic drugs on changes in the expression of DR5 and YinYang1(YY1) in MG-63 cells. Methods: The effects of treatment with rh-TRAIL alone and/or chemotherapeutic drugs on MG-63 cell growth inhibition and apoptosis were measured using the MTT assay, FACS analysis of Annexin V labeled cells, and the mRNA changes of DR5 and YY1 were detected by RT-PCR. Results: Rh-TRAIL protein inhibited the growth of MG-63 cells, and this inhibition was increased by adriamycin and IFN-γ. Adriamycin and IFN-γ significantly facilitated the induction of the expression of DR5 and reduced the expression of YY1. Conclusion: The apoptosis-inducing effect of rh-TRAIL in MG-63 cells was enhanced by chemotherapeutic drugs.