BACKGROUND: Previous studies have demonstrated that platelets play an important role in growth, invasion, and angiogenesis of a variety of tumors. Nevertheless, the prognostic role of platelet indices in hepatocellular carcinoma (HCC) has not been explored. The aim of this study was to explore the association between platelet indices and prognosis in HCC. METHOD: A total of 260 patients with HCC between January 2009 and December 2015 were retrospectively analyzed. The optimal platelet distribution width (PDW) cutoff value is identified by the receiver operating characteristic curve (ROC) curve. The relationship between PDW and clinicopathological features was assessed. The prognostic effects of PDW were assessed by using the Kaplan-Meier method and Cox regression model. RESULT: Elevated PDW level was significantly associated with portal hypertension, vascular invasion, and Child-Pugh grade. In addition, survival curve indicates that patients with high PDW levels have a worse prognosis than patients with low PDW levels (P< 0.001). Multivariate Cox regression analysis identified PDW as an independent factor of prognosis in HCC patients (hazard ratio: 4.460, 95% confidence interval: 2.308–8.619, P< 0.001). CONCLUSION: Elevated PDW may be a novel marker for predicting the prognosis of HCC, but further research is needed to validate our conclusions.