Objective To investigate the value of trophoblastic cell proliferation-related gene and interstitial cell apoptosis in the diagnosis of hydatidiform moles. Methods Immunohistochemical technique was used to detect the expressions of Ki67, Livin and Bcl-2 in trophoblast cells. TUNEL was used to detect apoptosis of villous stroma cells of 100 cases of hydatidiform moles (including 61 cases of complete hydatidiform moles and 39 cases of partial hydatidiform moles) and 40 cases of villous edema. Results The expression of Ki67 in the trophoblastic cells of the villous edema group, partial hydatidiform mole group and complete hydatidiform mole group gradually increased, the differences among the 3 groups were statistically significant (P < 0.05). There were no significant differences in the expression of Livin or Bcl -2 among the 3 groups (P > 0.05). There was a positive correlation between Ki67 expression and AI index (P < 0.05). Conclusions The detection of Ki67 expression in trophoblastic cells and apoptosis in villous stroma cells can be used for the diagnosis and classification of villous edema, partial hydatidiform mole and complete hydatidiform mole.