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Minjun Liao,1,2,* Pu Chen,1,* Yan Liao,3 Jun Li,1 Wenmin Yao,1 Tian Sun,1 Weijia Liao,1 Lili Su4 1Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of China; 2Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Disease Prevention and Control Center of Guilin, Guilin, Guangxi, People’s Republic of China; 4Department of Clinical Laboratory, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi, People’s Republic of China *These authors contributed equally to this work Background: At present, the predictive ability of the prognostic indicator of hepatocellular carcinoma (HCC) is still limited. This study aims to analyze the relationship between the preoperative high-sensitivity C-reactive protein to lymphocyte ratio (HCLR) and the clinicopathologic characteristics of HCC. Patients and methods: A total of 229 HCC patients undergoing surgical resection were retrospectively analyzed. The majority of the patients (132/229) had tumors larger than 5 cm, and 45 out of 229 had more than one tumor focus. Receiver operating characteristic curve analysis was used to decide the cutoff value of HCLR. The overall survival (OS) and progression-free survival (PFS) rates were evaluated by adopting the Kaplan–Meier method. Results: The cutoff value of HCLR for the best discrimination of HCC prognosis was 1.3 with a sensitivity of 75.5% and a specificity of 71.8%. The area under the receiver operating characteristic curve was 0.791 (95% CI, 0.731–0.840). Preoperative HCLR at a high level (>1.3) was positively correlated with large tumor size, TNM stage, microvascular invasion, and recurrence. The mean OS and PFS in patients with HCLR >1.3 were significantly shorter than in those with HCLR ≤1.3. Univariate and multivariate analyses revealed the HCLR was an independent predictor of OS