Abstract: In order to comprehensively evaluate the risk of α-particle irradiation, the biological effects of α-particle radiation combined with alcohol on hepatocytes was studied. The testing indicators which were the cell cycle, cell migration and cell invasion, as well as the mRNA expression were compared among the α-particle exposure group, the alcohol group,  and the combined factor group. Compared with the control group, the number of migrating and invading cells in the combined group significantly increases, the mRNA expression of the tumor suppressor related genes p53 and cdh1 significantly decreases, and the protooncogene mdm2 significantly increases. Hepatocytes occurres malignant transformation effected with a certain amount of α-particle irradiation and alcohol. But the hepatocytes are more likely to malignant transformation induced by alcohol after the same dose α-particle exposure. Alcohol may play a helper role in inducing malignant transformation. It may be related to the E-cadherin on the surface of hepatocytes, the low expressions of this surface protein, which reduces the adhesion between cells, and promoting cell migration and invasion. Therefore, drinking habits of occupational personnel should be considered in evaluating the health effects of αparticle internal irradiation.