Aim To explore the effects of nuciferine on the expression of microRNA-33a-5p (miR-33a-5p) and ATP-binding cassette transporter A1/G1 (ABCA1/G1) in THP-1 derived macrophages. Methods Macrophages were derived from THP-1 monocytes by PMA. Macrophages were randomly divided into four groups:normal cells, cells incubated with oxidized low density lipoprotein (ox-LDL), cells treated with nuciferine, cells pretreated with nuciferine were incubated with ox-LDL. Macrophages were valued by red O staining. The expression of miR-33a-5p and ABCA1/G1 were determined by RT-PCR and Western blot. Results Compared with the normal cells, lipid droplets were increased while the expression of miR-33a-5p were downregulated and ABCA1/G1 were upregulated in the cells incubated with ox-LDL. Compared with the normal cells, lipid droplets had no change while the expression of miR-33a-5p were downregulated and ABCA1/G1 were upregulated significantly in the cells treated with nuciferine. Compared with the cells incubated with ox-LDL, lipid droplets were dramaticlly decreased while the expression of miR-33a-5p were downregulated and ABCA1/G1 were upregulated significantly in the cells treated with nuciferine and ox-LDL. Conclusions Nuciferine downregulates miR-33a-5p expression and upregulates ABCA1/G1 expression in THP-1 derived macrophages and decreases the degree of foam formation.