Purpose.　To　explore　the　relationship　between　the　death　receptor　(DR)　and　the　pathological　progression　of　Kashin-Beck　disease　(KBD).　Design.　KBD　cartilage　samples　were　collected　from　15　patients　diagnosed　according　to　the　＂National　Diagnostic　Criteria　of　KBD＂　in　China.　In　vitro　monolayer　chondrocytes　were　cultured　in　complete　medium.　Caspase-3　and　caspase-8　activities　in　chondrocytes　were　analyzed　using　a　kit.　Nuclear　morphology　was　observed　by　Hoechst　33258　staining,　apoptosis　was　verified　by　flow　cytometry　analysis,　and　DR　molecules　were　detected　using　Western　blotting　and　quantitative　real-time　reverse　transcription　polymerase　chain　reaction　analysis.　Results.　Early　apoptotic　rates　of　KBD　and　osteoarthritis　(OA)　chondrocytes　were　higher　than　those　of　normal　control　(NC)　cells.　Excessive　apoptotic　nuclei　were　observed　in　OA　and　KBD　cells　after　Hoechst　33258　staining.　Activities　of　both　caspase-3　and　caspase-8　were　higher　in　KBD　and　OA　cells　than　in　NC　cells.　The　average　DR4　mRNA　level　in　KBD　cells　was　3.301-fold　higher　than　that　in　NC　cells,　Fas-associating　protein　with　death　domain　(FADD)　transcript　level　in　KBD　cells　was　2.528-fold　higher　than　that　in　NC　cells.　Western　blot　analyses　showed　that　FAS,　DR4,　DR5,　caspase-3,　and　FADD　were　upregulated　in　the　KBD　and　OA　groups　compared　with　the　NC　group.　High　expression　of　caspase-8　in　KBD　compared　with　NC　was　verified,　whereas　cellular　FLICE-inhibitory　protein　(c-FLIP)　in　KBD　was　significantly　downregulated.　Conclusions.　KBD　and　OA　chondrocytes　showed　obvious　FADD-caspase-dependent　apoptosis,　which　is　related　to　the　DR　pathway.　Apoptosis　in　KBD　articular　cartilage　is　mainly　related　to　FAS/DR4-FADD-caspase　signaling,　and　OA　is　associated　with　FAS/DR4/DR5-FADD-caspase　signaling.