Accumulating evidences have shown that microRNA-200c (miR-200c) expression is associated with the prognosis of many types of human cancer. However, the prognostic value of miR-200c in hepatocellular carcinoma (HCC) is still unknown. In the present study, the expression of miR-200c in paired HCC and adjacent non-tumor tissues from 148 patients was determined by quantitative real-time PCR (qRT-PCR), and we analyzed its association with clinicopathological characteristics and prognosis of HCC patients. Our results showed that the expression of miR-200c was significantly decreased in HCC tissues compared with adjacent non-tumor tissues (P < 0.0001). Correlation analysis showed that miR-200c expression was significantly associated with tumor size (P = 0.021), serum AFP level (P = 0.016), TNM stage (P = 0.019) and vein invasion (P = 0.026). Patients with lower miR-200c expression had significantly worse overall survival (OS, P = 0.023) and recurrence-free survival (RFS, P = 0.002). The multivariate Cox regression analysis revealed that miR-200c expression was an independent prognostic factor for OS (hazard ratio (HR) [95% CI] = 2.226 [1.235–4.012], P = 0.008) and RFS (HR [95% CI] = 2.662 [1.618–4.38], P < 0.001). In conclusion, our results suggest that the miR-200c expression was significantly down-regulated and associated with poor prognosis in HCC.