Romosozumab, a monoclonal antibody targeting sclerostin, is an effective anabolic therapy for patients with severe osteoporosis at very high fracture risk. Its safety profile has been considered favorable, and to our knowledge, no previous reports of serious liver injury have been associated with clinical doses of romosozumab. We report a rare case of drug-induced liver injury with autoimmune-like features temporally associated with romosozumab therapy. A 72-year-old woman developed marked elevations in aminotransferases after 3 monthly doses of romosozumab, with liver enzymes exceeding 20 times the upper limit of normal. Extensive evaluation excluded viral, metabolic, and other autoimmune liver diseases. Liver histology demonstrated portal inflammation with eosinophils, periportal necroinflammatory activity, and centrilobular necrosis, compatible with drug-induced liver injury. Autoimmune-like features, including smooth-muscle antibody positivity, were present, while serum IgG levels remained within the normal range. Causality assessment using the Roussel Uclaf Causality Assessment Method yielded a score of 6, indicating a probable association. Transaminase levels improved incompletely after drug withdrawal and normalized only after corticosteroid therapy, with relapse following early taper and sustained remission after prolonged treatment. This case suggests that, although rare, immune-mediated liver injury may occur in association with romosozumab therapy and highlights the importance of clinical awareness.