Objective To investigate the relationship between serum CA19-9 level and microvascular invasion (MVI) of primary hepatocellular carcinoma. Methods 271 patients with primary hepatocellular carcinoma who underwent complete radical resection in Nanchong Central Hospital from April 2009 to December 2013 were collected. Age, sex, child Pugh grade, serum AFP level, CEA level, CA19-9 level, tumor number and Ishak grade were analyzed by continuous variable and binary variable analysis respectively. The correlation between clinicopathological parameters and microvascular invasion was analyzed by logistic regression analysis and Pearson's substance 2 test to identify independent predictors significantly associated with microvascular invasion. Results Univariate analysis showed that among the variables predicting microvascular invasion of liver cancer, gender, tumor size, tumor number, AFP and CA19-9 were significantly correlated with microvascular invasion of liver cancer (P＜0.05). Multivariate analysis showed that tumor number, tumor size and CA19-9 were independent preoperative risk factors for microvascular invasion of hepatocellular carcinoma (P＜0.05). Conclusion Serum CA19-9 is an independent risk factor for preoperative prediction of microvascular invasion of primary hepatocellular carcinoma.