Objective:To explore the early clinical diagnostic indicators in patients with primary hepatocellular carcinoma (HCC) combined with macrovascular invasion.Methods:The clinical data of 180 cases of HCC diagnosed by histopathology examination in the Second Affiliated Hospital of Chongqing Medical University from 2012 to 2019 were retrospectively analyzed. The factors influencing the development of macrovascular invasion in HCC patients were analyzed. The receiver operating characteristic curve (ROC curve) was used to evaluate the sensitivity and specificity.Results:Serum C-reactive protein (CRP) level was significantly correlated with various clinical characteristics of HCC patients, including the maximum tumor diameter, tumor number, and macrovascular invasion. Further analysis of the risk factors showed that serum direct bilirubin and CRP were independent risk factors for macrovascular invasion in HCC patients, with odds ratios of 1.747 (95% CI 1.119-2.728, P = 0.014) and 2.376 (95% CI 1.495-3.775, P < 0.001). ROC curve analysis showed that serum CRP, direct bilirubin, and the combination of the both had certain diagnostic value for hepatocellular carcinoma combined with macrovascular invasion. The area under the curve, sensitivity and specificity was 0.724, 0.668, 0.743, 79.1%, 70.1%, 79.1%, and 61.9%, 62.8%, 67.3%, respectively. Conclusion:The combination of CRP with direct bilirubin can be used as an important clinical diagnostic indicator for early diagnosis and prevention of hepatocellular carcinoma combined with macrovascular invasion.