Objective To investigate the relationship of HMGA2 expression with clinicopathological parameters and prognosis in primary hepatocellular carcinoma. Methods The clinical data of 120 patients with hepatocellular carcinoma who underwent surgical resection from January 2010 to January 2013 in our hospital were collected. Immunohistochemical method was used to detect the expression of HMGA2 protein in cancer tissues, adjacent tissues and normal liver tissues of the resected specimens, and the clinicopathological parameters were recorded and followed up. The relationship between the positive expression of HMGA2 protein and clinical pathological parameters and prognosis of the patie nts was analyzed. Results Immunohistochemical staining showed that the positive expression of HMGA2 protein was brown or tan, mainly located in the nuclei of tumor cells. The positive rate of HMGA2 protein in HCC tissues was higher than in adjacent tissues and normal liver tissues (P < 0.05). The expression of HMGA2 protein was higher in patients with hepatocellular carcinoma in high clinical stage, hilar lymph node metastasis and intrahepatic metastasis (P < 0.05). Multivariate analysis showed that clinical stage, hepatic hilar lymph node metastasis and intrahepatic metastasis were independent risk factors of HMGA2 protein expression (P < 0.05). The difference of 3-year survival rate between the two groups was statistically significant (P < 0.05). Conclusions The prognosis of patients with positive HMGA2 protein is poor, and HMGA2 protein can be used as a potential index to judge the prognosis of patients with HCC.