Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. Methods: A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. Results: Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (${leq}4$) (P=0.01). Age ${leq}65$, NLR>4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). Conclusions: High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.