Objective To study the effect of lovastatin on the expression and activity of β-site APP cleaving enzyme (BACE1). Methods The SH-SY5Y cells were treated by lovastatin. Cell viability was assessed by MTT assay, and the levels of cholesterol were assayed spectrophotometrically, and the activity of BACE1 was detected by fluorometric assay, and the expression level of BACE1 was detected by Western Blot. Results Compared with the control group, the cholesterol levels were decreased by 33.0% (3.33 vs. 4.97; F=5.13, P =0.020) and the activity of BACE1 was reduced by 13.8% (343.14 vs. 398.22; F=3.773, P =0.035) after 24h treatment of 5μmol/L lovastatin; the cholesterol levels were decreased by 49.2% (2.65 vs. 5.22; F=12.239, P =0.001) and the activity of BACE1 was reduced by 38.0% (274.75 vs. 443.14; F=13.610, P <0.01). Treatment with 5μmol/L lovastatin,for 48 h did affect the expression level of BACE1. Conclusions Lovastatin do not affect the expression level of BACE1, but may inhibit its activity and decrease the cholesterol level, thus providing a new approach to prevent or treat Alzheimer's disease (AD).