Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a major cause of cancer-related mortality worldwide. This study aimed to evaluate the safety and efficacy of hepatic artery infusion chemotherapy (HAIC) combined with camrelizumab and apatinib in patients with advanced HCC. A retrospective analysis was conducted on patients with advanced HCC who received either camrelizumab plus apatinib (N = 65) or HAIC combined with camrelizumab and apatinib (N= 65). Objective response rate (ORR), disease control rate (DCR), serum tumor marker levels, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Baseline clinical characteristics were comparable between the two groups. Compared with camrelizumab plus apatinib alone, treatment with HAIC combined with camrelizumab and apatinib achieved significantly higher ORR and DCR and was associated with more favorable post-treatment serum AFP, CEA, and CA19-9 levels. Treatment-related adverse events were generally manageable. At the final follow-up, median PFS was 15 (2–24) months in the camrelizumab plus apatinib group and 15 (8–30) months in the HAIC plus camrelizumab plus apatinib group, respectively. Median OS of the two groups was 20 (6–27) months and 21 (10–30) months, respectively. Based on the Kaplan-Meier analysis, patients receiving the trimodality therapy demonstrated significantly prolonged PFS and OS. Together, HAIC combined with camrelizumab and apatinib demonstrated favorable efficacy and acceptable safety in patients with advanced HCC. This combination regimen may represent a promising therapeutic strategy for advanced HCC.