OBJECTIVE The most common haematological malignancy is leukaemia. Differentiation induction is considered as one of the effective therapies for leukemia. Piperine, an alkaloid extracted from piperaceae, has been reported to display a variety of pharmacological activities, including sedation, anti-inflammation and antitumor effects. This study was to investigate the effect of piperine on proliferation, differentiation and apoptosis of erythroleukemia K562 cells. METHODS Inhibition of cell growth was determined by trypan blue exclusion test; cell cycle and cell apoptosis were analyzed by FACS; induction of cell differentiation was confirmed by morphological observation, nitroblue tetrazolium (NBT) reduction assay and measurements of CD33 and CD14 expressions. RESULTS Piperine induced K562 cells to differentiate into macrophages/monocytes at 20 micromol/L or 40 micromol/L. After incubation with 40 mumol/L piperine for 3 d, the NBT reduction rate of K562 cells increased from (8.5+/-1.9)% to (76.7+/-5.3)%; after incubation with 20 mumol/L piperine for 3 d, the mean fluorescence intensity (MFI) of CD33 in K562 cells was decreased by 42.05% (P<0.01), whereas the MFI of CD14 was doubled (P<0.01). Piperine inhibited the proliferation of K562 cells in a dose-and time-dependent manner at a concentration of above 20 micromol/L. CONCLUSIONS Piperine can induce K562 cells to differentiate into macrophages/monocytes.