Background and Aims In recent years, targeted drug therapy has rapidly developed and become an important method for treating advanced hepatocellular carcinoma (HCC). However, the response rate of first-line targeted drug sorafenib in treating HCC is low, and improving clinical protocols for targeted drug therapy in HCC remains a challenging issue. This study was performed to investigate the clinical efficacy of apatinib combined with camrelizumab in treating intermediate to advanced HCC and its impact on patients' immune function and tumor markers.Methods The clinical data of 137 patients with unresectable intermediate to advanced HCC admitted between May and December 2022 were retrospectively analyzed. Among them, 61 patients were treated with oral apatinib alone (targeted group), and 76 received intravenous camrelizumab in addition to oral apatinib (targeted-immune group). The objective response rate (ORR) and disease control rate (DCR) of the two groups were compared; levels of T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺), alpha-fetoprotein (AFP), Golgi protein 73 (GP-73), and AFP-L3 were measured; liver and kidney function indicators and adverse reactions were monitored. A 12-month follow-up was conducted to assess the two groups' progression-free survival (PFS).Results Before treatment, there were no statistically significant differences in general data, liver and kidney function indicators, and immune and tumor marker levels between the two groups (all P>0.05). After treatment, the ORR and DCR in the targeted-immune group were higher than those in the targeted group (40.79% vs. 16.39%, P=0.02; 60.53% vs. 39.34%, P=0.014). The CD3⁺, CD4⁺, and CD4⁺/CD8⁺ levels in the targeted-immune group were higher, while CD8⁺ levels were lower than those in the targeted group (all P<0.05). AFP, GP-73, and AFP-L3 levels in the targeted-immune group were lower than those in the targeted group (all P<0.05). The total bilirubin and alanine aminotransferase levels in the targeted-immune group were lower than those in the targeted group (both P<0.05). The incidence of skin capillary hemangiomas was higher in the targeted-immune group than in the targeted group (42.11% vs. 18.03%, P<0.05). In contrast, the incidence of other adverse reactions did not differ significantly between the two groups (all P>0.05). After 12 months of follow-up, the median PFS in the targeted-immune group was significantly longer than that in the targeted group (10 months vs. 6 months, χ²=9.954, P<0.05).Conclusion Apatinib combined with camrelizumab in treating HCC can enhance T lymphocyte levels, reduce tumor marker levels, effectively prolong survival time, and have better efficacy than targeted therapy alone, with reasonable safety.