〔Abstract〕 Objective To investigate the effects of farnesyltransferase inhibitor(FTI) and geranylgeranyl transferase inhibitor(GGTI) on the proliferation of keratinocytes(KCs). Methods KCs were treated with different concentrations of FTI and GGTI. MTS analysis was used to analyze the effect of each treatment group on KCs cell proliferation. Flow cytometry was used to detect the effect of certain concentrations of FTI and GGTI on the cell cycle. Western blot was used to analyze the effects of certain concentrations of FTI and GGTI on the expressions of CyclinB1, CyclinE and P21, pAKT and pERK1/2 in each group. Results MTS showed that FTI and GGTI inhibited the proliferation of KCs in a concentration-dependent manner. The activity of KCs was the smallest in FTI(5 μmol/L) and GGTI(5 μmol/L), and the inhibition rates were 14.7% and 24.5%, respectively. The results of the flow cycle indicated that the FTI and GGTI retardation of KCs were not obvious in all phases of G1, G2 and S. Western blot results showed that FTI and GGT could down-regulate CyclinB1 and up-regulate the expression of P21 and CyclinE. At the same time, FTI and GGTI could promote the activation of P13 K-AKT signaling pathway and inhibit the activation of MAPKS-ERK1/2 signaling pathway. Conclusion FTI and GGTI have an inhibitory effect on the proliferation of primary KCs.