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The prognostic value of tissue and serum osteopontin (OPN) in hepatocellular carcinoma (HCC) remain controversial. The aim of present meta-analysis was to evaluate the prognostic value of OPN in patients with HCC.Eligible studies were systematically searched by PubMed, EMBASE, and Google scholar. A meta-analysis of 12 studies included 2117 cases was performed to estimate the association between OPN level and overall survival (OS), disease-free survival (DFS) in HCC patients. Subgroup analyses were also performed in the meta-analysis.The pooled data of studies showed that high OPN level was significantly associated with poor OS (hazard ratios [HR] 1.84; 95% confidence intervals [CI] 1.54–2.20; P= .000) and DFS (HR 1.67; 95% CI 1.40–1.98; P= .000) in HCC. Furthermore, in subgroup analysis, high tissue based OPN by immunohistochemistry detection and serum-based OPN by enzyme-linked immunosorbent assay (ELISA) detection were both significantly associated with OS (tissue: HR 1.88; 95% CI 1.53–2.31; P < .0001; serum: HR 2.38; 95% CI 1.58–3.59; P < .0001). Simultaneously, we also found that OPN expression was positively associated with stage (odds ratios [OR] 5.68; 95% CI 3.443–7.758), tumor size (Size≤5 cm vs >5 cm; OR 2.001; 95% CI1.036–3.867).The current evidence indicates that OPN could serve as a prognostic biomarker and a potential therapeutic target for HCC.