Objective: 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). 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). Conclusions: Hypoxia up-regulates YAP1 in osteosarcoma cells in a HIF-1α dependent manner. YAP1 may promote CDDP resistance of osteosarcoma cells by activating STAT3.