Aims: Biomechanical reactivity is a special property of chondrocytes and mechanical stress can affect the development of cartilage. Primary cilia have been proved a cellular sensory which can detect physical and chemical stimuli extracellular and initiate multiple signaling transduction. Autophagy is an important environmental adaptive mechanism for cells maintenance of homeostasis. The aims of this study were to detect whether there is an interaction between primary cilia and autophagy in the regulation of mechanical stress-mediated cartilage development and to explore the underlying mechanism. Main methods: In this study, chondrocytes were treated with cyclic tensile strain (CTS) by the four-point bending system. Chondrocytes viability, proliferation and differentiation capacities were analyzed by western blot and live/dead assays after CTS of different intensities. Meanwhile, primary cilia incidence and length changes, and autophagy expression were detected by immunofluorescence staining. The primary cilia and autophagy interaction regulation and the underlying mechanism were detected by immunofluorescence double staining and western blot. Key findings: Mechanical stress could affect chondrocytes proliferation, phenotype and viability in an intensity dependent manner. The incidence and length of primary cilia as well as autophagy expression could be regulated by CTS. The integrity of primary cilia structure is vital for mechanical stress regulated ERK/mTOR signaling transduction and autophagy expression in chondrocyte. Significance: These findings indicate that mechanical stress could affect the interaction between primary cilia and autophagy and help to reveal the underlying mechanism of stress regulated cartilage development.