Background: Peripheral blood monocyte count is an easily assessable parameter of systemic inflammatory response. The aim of this study was to determine whether monocyte count was prognostic in hepatocellular carcinoma (HCC) following hepatic resection. Methods: We retrospectively reviewed 351 patients with HCC treated with hepatic resection from 2006 to 2009. Preoperative absolute peripheral monocyte count, demographics, and clinical and pathological data were analyzed. Results: On univariate and multivariate analysis, elevated monocyte counts (>= 545/mm(3)), tumor size >= 5 cm, non-capsulation, and multiple tumors were associated with poor disease-free survival (DFS) and overall survival (OS). The 1-, 3- and 5-year DFS rates were 58%, 41% and 35%, respectively, for patients with monocyte counts <545/mm(3), and 36%, 23% and 21% for patients with monocyte counts >= 545/mm(3). Correspondingly, the 1-, 3-and 5-year OS rates were 79%, 53% and 46% for monocyte counts <545/mm(3), and 64%, 36% and 29% for monocyte counts >= 545/mm(3). Subgroup analysis indicated that DFS after hepatic resection in hepatitis B virus (HBV)-infected patients was significantly better in those with a peripheral blood monocyte counts <545/mm(3), but it did not differ between patients without HBV infection. In addition, DFS was significantly better for patients with a peripheral blood monocyte count <545/mm(3), whether or not cirrhosis was present. Patients with elevated monocyte counts tended to have larger tumors. Conclusions: Elevated preoperative monocyte count is an independent predictor of worse prognosis for patients with HCC after hepatic resection, especially for those with HBV infection. Postoperative adjuvant treatment might be considered for patients with elevated preoperative monocyte counts.