Objectives To investigate the role of YAP in cyclic mechanical stress induced up-regulation of HIF-1 alpha in rat cartilage chondrocytes. Results Our in vitro and in vivo experiments demonstrated that cyclic mechanical stress promoted HIF-1 alpha and YAP proteins expression in a magnitude dependent manner. Cyclic mechanical stress at 4000 mu strain exhibited most significant effect in promoting HIF-1 alpha and YAP up-regulation. Activation of YAP using LPA significantly promoted HIF-1 alpha stabilization and expression, while YAP siRNA treatment suppressed the up-regulation of HIF-1 alpha induced by cyclic mechanical stress. Conclusion Our results indicated that cyclic mechanical stress promoted HIF-1 alpha stabilization and YAP is involved in mechanical stress induced HIF-1 alpha up-regulation.