【Abstract】Objective：To evaluate the efficacy and safety of targeted therapy plus immunotherapy ± Transcatheter Arterial Chemoembolization (TACE)/radiotherapy for conversion therapy in initially unresectable intermediate-to-advanced hepatocellular carcinoma (HCC). Method: We retrospectively analyzed 20 patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC treated with targeted therapy and immunotherapy; 19 received concurrent TACE and 4 received radiotherapy. The evaluation indicators include Objective Response Rate (ORR), microscopic margin-negative (R0) resection rate and safety. Results: The overall ORR and Disease Control Rate (DCR) were 55% and 85%, respectively. Four patients (20%) successfully underwent R0 resection, with 2 achieving Major Pathological Response (MPR). The incidence of grade ≥3 adverse events(AEs ) was 20%, primarily immune-related liver injury. At a median follow-up of 18.3 months, 3 of the 4 resected patients remained recurrence-free 12 months post-surgery. Conclusion: The multimodal approach centered on targeted combined immunotherapy has a significant ability to downstage advanced HCC. The R0 resection rate is 20%, and the pathological remission is remarkable with controllable safety. Due to the limited sample size, the long-term benefits still need to be verified with a larger sample. 【Keywords】Hepatocellular Carcinoma; Conversion Therapy; Targeted Therapy Combined with Immunotherapy; TACE; Radiotherapy