Autophagy is a fundamental cell biological process that confers stress tolerance, limits damage, and sustains viability under adverse conditions. Defective autophagy is associated with diverse diseases. The study aimed to investigate the relationship between UNC51-like kinase 1 (ULK1) expression and clinicopathological characteristics as well as survival in patients with hepatocellular carcinoma (HCC). Expression levels of ULK1 in 55 paired HCC and paracancerous tissues were examined using immunohistochemistry. Although not statistically significant, the expression of ULK1 in adjacent peritumoural tissue was lower than those in HCC tissues (P = 0.113). Expression level of ULK1 was significantly associated with tumor size (P = 0.015) after adjusted for age, sex, histologic grade, cirrhosis and TNM. Survival analysis showed that patients with high ULK1 expression had worse survival time than those with low ULK1 expression (hazard rate = 2.684, 95% CI 1.029-7.006, P = 0.044). The findings of the present study provide evidence that ULK1 represents a potential novel prognostic biomarker for HCC patients and may play an important role during the progression of HCC.