HALP score consisting of hemoglobin content, albumin content, lymphocyte count, and platelet count can comprehensively evaluate the inflammatory response and nutritional status. Many researchers have indicated that the HALP score is an effective predictor of the overall prognosis of various tumors. However, there is no relevant research to suggest whether the HALP score can predict the prognosis of patients with hepatocellular carcinoma (HCC). We retrospectively analyzed 273 HCC patients who underwent surgical resection. Hemoglobin content, albumin content, lymphocyte count, and platelet count in peripheral blood were measured for each patient. The relationship between the HALP score and overall survival (OS) was investigated. With a mean of 56.69 ± 1.25 months follow-up, the 1-, 3-, and 5-year OS was 98.9%, 76.9%, and 55.3% for all patients, respectively. HALP scores (HR=1.708, 95% CI=1.192-2.448, P=0.004) were significant independent risk factors of OS. The 1-, 3-, and 5-year OS were 99.3%, 84.3%, and 63.4% for patients with high HALP scores; and 98.6%, 69.8%, and 47.5% for patients with low HALP scores, respectively (P=0.018). In TNM I-II stage patients, compared with high HALP scores, low HALP scores have worse OS (P=0.039). In AFP positive patients, compared with high HALP scores, low HALP scores have worse OS (P=0.042). Our research showed the preoperative HALP score is an independent predictive factor of overall prognosis, and a low HALP score indicates a worse prognosis in HCC patients who underwent surgical resection.