Aim To investigate the impact of bakuchiol (BAK) on lipid accumulation in macrophage-derived foam cell and explore the underlying mechanisms. Methods MTT assay was used to determine the non-toxic concentration of BAK on foam cell. Oil red O staining, NBD cholesterol, and Dil-ox-LDL were used to assess lipid accumulation in foam cell. RT-qPCR and Western blot were utilized to measure mRNA and protein expression, respectively. Results BAK promoted cholesterol effux and reduced lipid accumulation in foam cell. BAK upregulated the mRNA and protein expression levels of ATP-binding cassette transporter A1 (ABCA1) and concurrently downregulated the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with the ERK1/2 activator Ro 67-7476 resulted in decreased ABCA1 protein expression compared with the BAK-treated group. Conclusion BAK reduced lipid accumulation in foam cell by inhibiting ERK1/2 phosphorylation, upregulating ABCA1 expression, and promoting cholesterol efflux, thereby suppressing foam cell formation.