Objective To explore the clinical efficacy on downgrading transformation with immune and targeted regimens in initially unresectable advanced hepatocellular carcinoma in a real-world setting. Methods The clinical data of 5 patients with unresectable advanced liver cancer admitted to Yancheng First Hospital Affiliated to Nanjing University Medical School from February 2019 to October 2020 were retrospectively analyzed. Preoperative combined treatment of immune + targeted + local therapy was applied, radical surgery was performed after the tumor reached the transformation standard, and systemic therapy was continued after the surgery to prevent tumor recurrence and metastasis. Results All 5 patients had successful down-stage transformation and were well tolerated by preoperative systemic treatment for 3-9 cycles. The operation time was 261 min (200-320 min), the intraoperative blood loss was 540 ml (200-800 ml),and the intraoperative blood transfusion was 304 ml (0-580 ml). Routine pathology showed varying proportions of residual carcinoma. During the follow-up period of 22.2 weeks (12-31 weeks), there was no tumor recurrence or metastasis,and no perioperative death. Conclusions For patients with unresectable advanced liver cancer, the down-stage transformation strategy of immunotherapy combined with targeted local therapy is worthy of expectation.