Objective：This study aims to investigate the effect of yes associated protein 1（YAP1）on cisplatin（CDDP）sesitivity of osteosarcoma cells under hypoxia and its underlying mechanism. Methods：Flow cytometry and CCK-8 were used to detect the CDDP sensitivity of osteosarcoma cells. Western blot was used to detect the expression of hypoxia inducible factor-1α（HIF-1α），YAP1，signal transducer and activator of transcription 3（STAT3）and p-STAT3 protein in human osteosarcoma cell line MG-63 under normoxic and hypoxic conditions after transfection with HIF-1 α-siRNA，YAP1-siRNA and STAT3-siRNA. Results：YAP1 was highly expressed in MG-63 cells after hypoxia（P < 0.05）. Overexpression of YAP1 significantly reduced the sensitivity of MG-63 cells to CDDP under hypoxic condition（P < 0.01）. The apoptosis rate of osteosarcoma cells was significantly increased（P < 0.01）and the sensitivity of osteosarcoma cells to CDDP was increased（P < 0.01）under hypoxic condition after transfection with YAP1-siRNA. The expression of p-STAT3 in MG-63 cells was significantly down-regulated after inhibiting YAP1 expression（P < 0.01）. Silencing STAT3 significantly increased the sensitivity of MG-63 cells to CDDP under hypoxia（P < 0.01）. Silencing HIF-1α significantly inhibited hypoxia-induced up-regulation of YAP1（P < 0.01），and incresed the sensitivity of MG-63 cells to CDDP. Conclusion：Hypoxia up-regulates YAP1 in osteosarcoma cells in a HIF-1α dependent manner. YAP1 may promote CDDP resistance of osteosarcoma cells by activating STAT3.