This study presents a novel photothermal therapy approach using near-infrared (NIR)-responsive gold nanorods (Cit-AuNRs) conjugated with a TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) to treat osteoarthritis (OA). The system activates TRPV1 upon NIR irradiation, which suppresses chondrocyte ferroptosis and alleviates OA progression. The conjugation of the antibody with Cit-AuNRs does not significantly alter the morphology or physicochemical properties of the nanorods. Under NIR irradiation, the system exhibits good biocompatibility and photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activates TRPV1, reduces cartilage degradation, and suppresses chondrocyte ferroptosis. The treatment also alleviates osteophyte formation and subchondral bone sclerosis. Furthermore, it improves physical activities and reduces pain in mice with DMM-induced OA. The study demonstrates that Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, offering a potential therapeutic strategy for OA treatment. The system is safe and shows no significant toxicity in vivo. The findings suggest that targeting TRPV1 with NIR-responsive nanomaterials could be a promising approach for OA therapy.This study presents a novel photothermal therapy approach using near-infrared (NIR)-responsive gold nanorods (Cit-AuNRs) conjugated with a TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) to treat osteoarthritis (OA). The system activates TRPV1 upon NIR irradiation, which suppresses chondrocyte ferroptosis and alleviates OA progression. The conjugation of the antibody with Cit-AuNRs does not significantly alter the morphology or physicochemical properties of the nanorods. Under NIR irradiation, the system exhibits good biocompatibility and photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activates TRPV1, reduces cartilage degradation, and suppresses chondrocyte ferroptosis. The treatment also alleviates osteophyte formation and subchondral bone sclerosis. Furthermore, it improves physical activities and reduces pain in mice with DMM-induced OA. The study demonstrates that Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, offering a potential therapeutic strategy for OA treatment. The system is safe and shows no significant toxicity in vivo. The findings suggest that targeting TRPV1 with NIR-responsive nanomaterials could be a promising approach for OA therapy.