This study aimed to assess the therapeutic effect of immune checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma (uHCC) and investigate the correlation between surrogate endpoints and overall survival (OS). A systematic literature search included phase I, II, and III clinical trials comparing ICIs to placebo or other therapies for uHCC treatment. Correlations between OS and surrogate endpoints were evaluated using meta-regression analyses and calculating the surrogate threshold effect (STE). The correlation analysis showed a weak association between OS and progression-free survival (PFS), with an R value of 0.352 (95% CI: 0.000-0.967). However, complete response (CR) exhibited a strong correlation with OS (R = 0.905, 95% CI: 0.728-1.000). Subgroup analyses revealed high correlations between OS and PFS, CR, stable disease (SD), and DC in phase III trials (R: 0.827-0.922). For the ICI + IA group, significant correlations were observed between OS and SD, progressive disease (PD), and grade 3-5 immune-related adverse events (irAEs) (R: 0.713-0.969). Analyses of the correlation between survival benefit and risk of mortality across various time points showed a strong association within the first year (R: 0.724-0.868) but a weak association beyond one year (R: 0.406-0.499). In ICI trials for uHCC, PFS has limited utility as a surrogate endpoint for OS, while CR exhibits a strong correlation with OS. Subgroup analyses highlight high correlations between OS and PFS, SD, and DC in phase III trials. Notably, the ICI + IA group shows significant associations between OS and SD, PD, and grade 3-5 irAEs. These findings offer valuable insights for interpreting trial outcomes and selecting appropriate endpoints in future clinical studies involving ICIs for uHCC patients.