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The objective of the present study was to investigate the association between zinc finger protein (ZNF) 689 expression and the clinicopathological features and prognosis of hepatocellular carcinoma (HCC). A total of 102 paired HCC and paired non‑cancerous tissues, and 16 normal liver tissues were collected. ZNF689 expression was examined in HCC tissues, paired‑noncancerous tissues, and normal liver tissues using RT‑qPCR and immunohistochemistry analysis, and the association between ZNF689 expression and HCC prognosis was analyzed using the Kaplan‑Meier method. ZNF689 expression was not significantly different between HCC tissues and paired‑noncancerous tissues (P=0.61). ZNF689 expression in HCC and paired‑noncancerous tissues was significantly increased compared with that in normal liver tissues (P<0.01). Positive expression of ZNF689 protein in HCC was significantly associated with a tumor size of ≥10 cm, tumor capsule infiltration, and microvascular invasion (P<0.05). Positive expression of ZNF689 was a prognostic factor for overall survival time [hazard ratio (HR):1.961; P=0.048] and progression‑free survival time (HR:1.902; P=0.041). ZNF689 maybe a novel predictor for prognosis of patients with HCC. [ABSTRACT FROM AUTHOR]