AIM: To evaluate human lens epithelium cell apoptosis and epithelial to mesenchymal transition (EMT) induced by femtosecond laser in femtosecond laser assisted cataract surgery (FLACS). METHODS: Sixty cataract patients with N2 to N3 stage according to the LOCS III were enrolled in this study and divided into three groups randomly: FLACS1 group (cataract surgery by FLACS with LenSx), FLACS2 group (cataract surgery by FLACS with LensAR) and manual group (cataract surgery by phacoemulsification). Patients in two FLACS groups performed anterior capsulotomy by LenSx or LensAR laser system. Patients in the manual group were performed continuous curvilinear capsulorrhexis (CCC) manually. The anterior capsules were fixed right after moved out of eye. Hematoxylin-eosine staining, immunofluorescence staining and real-time PCR were performed in order to observe human lens epithelium cells changes after cataract surgery. RESULTS: The capsule cutting edge was shown irregularity and roughness in two FLACS groups and smooth edge in manual capsulotomy by pathologic staining. Irregularities of the cell configuration with partly swollen and destroyed nuclei were observed in two FLACS groups. Femtosecond laser could induce a significantly higher cell apoptosis in human lens epithelium cell than manually performed CCC (P<0.05). Lens epithelium cells apoptosis were correlated with femtosecond laser duration according to Pearson correlation analysis. Decreased N-cadherin expression, alpha-SMA and FSP-1 level in two FLACS groups showed the inhibition of cell EMT. CONCLUSION: Femtosecond laser may affect the apoptosis and EMT of lens epithelium cells which are under the peeled central lens capsule.