Aim To investigate the effect and mechanism of miR-19b on ATP binding cassette transporter A1 （ABCA1） mediated intracellular cholesterol efflux. Methods After transfected miR-19b mimic and inhibitor into THP-1 derived macrophage, cholesterol efflux was detected with liquid scintillator, and intracellular lipid droplet was stained with oil red O. The binding of miR-19b with ABCA1 3′UTR was analyzed with bioinformatics websites. MiR-19b binding to ABCA1 3′UTR was confirmed with luciferase reporter assay. ABCA1 expression was measured by Western bolt. Results MiR-19b dramatically suppressed macrophage cholesterol efflux, resulting in excessive lipid accumulation and foam cells formation. The exactly opposite results were observed by anti-miR-19b in THP-1 macrophage. MiR-19b bound to the 3110-3116 sites within ABCA1 3′UTR, and their binding free energy was very low. MiR-19b potently inhibited the luciferase activity and macrophage ABCA1 expression. Conclusions MiR-19b targets ABCA1 and inhibits intracellular cholesterol efflux, causing excessive lipid accumulation in macrophage.