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Biomarkers for hepatocellular carcinoma (HCC) following curative resection are not currently sufficient for prognostic indication of overall survival (OS) and disease-free survival (DFS).The aim of this study was to investigate the prognostic performance of osteopontin (OPN),matrix metalloproteinase 7 (MMP7),and pregnancy specific glycoprotein 9 (PSG9) in patients with HCC.A total of 179 prospective patients with HCC provided plasma before hepatectomy.Plasma OPN,MMP7,and PSG9 levels were determined by enzyme-linked immunosorbent assay.Correlations between plasma levels,clinical parameters,and outcomes (OS and DFS) were overall analyzed.High OPN (≥ 149.97 ng/mL),MMP7 (≥ 2.28 ng/mL),and PSG9 (≥ 45.59 ng/mL) were prognostic indicators of reduced OS (P ＜ 0.001,P ＜ 0.001,and P =0.007,respectively).Plasma PSG9 protein level was an independent factor in predicting OS (P=0.008) and DFS (P=0.038).Plasma OPN + MMP7 + PSG9 elevation in combination was a prognostic factor for OS (P ＜ 0.001).OPN was demonstrated to be a risk factorassociated OS in stage Ⅰ patients with HCC and patients with low α-fetoprotein levels (＜ 20 ng/mL).These findings suggested that OPN,MMP7,PSG9 and their combined panels may be useful for aiding in tumor recurrence and mortality risk prediction of patients with HCC,particularly in the early stage of HCC carcinogenesis.