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). Methods: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 among them. The evaluation indicators include objective response rate(ORR),microscopic margin-negative(R0) resection rate and safety. Results:The overall ORR and the disease control rate were 55% and 85%,respectively. Four patients(20%) successfully underwent R0 resection,with 2 achieving major pathological response. The incidence of grade ≥3 adverse events 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.