This study was aimed to investigate the anti-proliferation effect of interferon-alpha (IFN-alpha) on leukemic U937 cells and its mechanism. The U937 cells were given with various concentrations of IFN-alpha (500, 1 000, 2,000, 3,000 and 4,000 U/L) and at different time (0, 12, 24, 36, 48 hours), the inhibitory ratio was measured by MTT assay, apoptosis rate was detected by flow cytometry (FCM), the expression of cell cycle-associated cyclin E mRNA was measured by RT-PCR. The results showed that IFN-alpha (2,000 U/L) could cause apoptosis, after being treated by various concentrations of IFN-alpha, the growth of U937 cells was inhibited significantly, the apoptosis rate was 25.82% - 70.54% (P < 0.01), the cycle-associated cyclin E mRNA expression decreased, the growth of U937 cells was significantly inhibited, the suppression of U937 by IFN-alpha was both in time-and dose-dependent manner. It is concluded that IFN-alpha has apparent anti-proliferation and apoptosis-inducing effects on U937 cells. These results will provide strong laboratory evidence for IFN-alpha clinical application in leukemia therapy.