Objective <p>Soluble programmed cell death-ligand 1 (sPD-L1) and soluble programmed cell death 1 (sPD-1) interact to promote tumor immune evasion and play important roles in the progression of hepatocellular carcinoma (HCC). Nevertheless, their clinical value in HCC patients remains controversial. Therefore, the present meta-analysis aimed to assess the diagnostic and prognostic value of sPD-L1 or sPD-1 for HCC comprehensively.</p> Methods <p>A systematic search was performed in Web of Science, PubMed, Embase, and the Cochrane Library up to April 2025. Studies comparing sPD-1 or sPD-L1 levels between HCC patients and controls or assessing the associations of sPD-1 or sPD-L1 levels with prognosis in HCC patients were collected.</p> Results <p>Fourteen studies involving 1420 cases were included. Elevated sPD-L1 levels were observed in HCC patients compared with controls [standardized mean difference (SMD) (95% confidence interval (CI)): 2.655 (0.351, 4.959), <i>P</i> = 0.020]. A high sPD-L1 level was linked to reduced progression-free survival (PFS) [hazard ratio (HR) (95% CI): 2.807 (1.470, 5.361), <i>P</i> = 0.002], and it tended to be related to shortened overall survival (OS) in HCC patients, although the difference was not statistically significant [HR (95% CI): 1.817 (0.923, 3.576), <i>P</i> = 0.080]. Moreover, there was no association between sPD-1 levels and PFS [HR (95% CI): 1.028 (0.511, 2.069), <i>P</i> = 0.940] or OS [HR (95% CI): 1.017 (0.637, 1.624), <i>P</i> = 0.940)] in HCC patients. All included studies were of high quality. No publication bias was observed.</p> Conclusion <p>sPD-L1, but not sPD-1, may be a diagnostic and prognostic biomarker that contributes to the management of HCC.</p>