Ferroptosis is an iron-dependent form of regulated cell death triggered by the toxic accumulation of lipid peroxides on cell membranes. Recent studies highlight its pivotal role in tumor suppression, offering new opportunities for cancer therapy. JRIPS-C2, a natural compound isolated from the traditional Chinese herb Ligusticum chuanxiong Hort, has been identified as an anti-cancer agent. However, its role in bladder cancer and underlying mechanisms remain largely unknown. In the study, we investigated the effect of JRIPS-C2 on human bladder cancer cell lines 5637 and T24. JRIPS-C2 induced significant cell death, which was reduced by the ferroptosis inhibitors ferrostatin-1 and deferoxamine mesylate, but not by the apoptosis inhibitor Z-VAD-FMK (Z-VAD), the necroptosis inhibitor necrosulfonamide or the autophagy inhibitor  bafilomycin A1, suggesting that ferroptosis is the dominant pathway. Mechanistically, JRIPS-C2 enhanced lipid peroxidation by up-regulating ACSL4 and down-regulating GPX4, accompanied by dysregulation of intracellular iron homeostasis. These findings suggest that JRIPS-C2 acts as a ferroptosis inducer and may represent a promising candidate for the treatment of bladder cancer.