Abstract: Objective To investigate the effect of silencing LPXN expression by RNA interference on the proliferation and drug sensitivity of human acute monocytic leukemia SHI-1 cells in vitro. Methods Small interfering RNA (siRNA) sequences targeting LPXN were designed and transiently transfected in SHI-1 cells via Lipofectamine 2000, and the most efficient siRNA sequence for LPXN silencing was identified using Western blotting. The protein expression levels of LPXN, p-JNK, p-P38 MAPK and p-ERK were in the cells transfected with the selected siRNA were detected using Western blotting, and the cell proliferation changes were assessed using CCK-8 reagent. Results LPXN silencing by siRNA transfection resulted in significant proliferation suppression in SHI-1 cells with an inhibition rate of（27.04±2.05）% (P<0.05). Western blotting showed that treatment of the siRNA-transfected SHI-1 cells with 0-25 μmol/L curcumin or with 0-2.0 μmol/L Ara-C further increased the cell inhibition rate and obviously enhanced the expressions of p-P38 MAPK and p-JNK without significantly affecting p-ERK expression. Conclusions Down-regulation of LPXN expression by siRNA transfection can suppress the proliferation and increase the drug sensitivity of SHI-1 cells probably by activating JNK and P38 MAPK.