Abstract: Objective To evaluate the therapeutic effect of interferon alpha(IFN-α) on patients with chronic myeloproliferative neoplasm(MPN). Methods We retrospectively made an analysis of 110 advanced MPN patients diagnosed, including 76 essential thrombocytosis(ET) patients with or without JAK2V617F mutation and 34 polycythemia vera(PV) patients with JAK2V617F mutation. All patients received IFN-α or hydroxyurea(HU) therapy for more than 6 months. The clinical data of efficacy and side effects were observed and compared. Results The overall response rate(ORR) between IFN-α and HU treatment groups of ET and PV patients with JAK2V617F mutations had no significant difference(89.5% vs. 85.7%；87.5% vs. 83.3%, P>0.05), but the 5-year progression-free survival(PFS) rate of IFN-α and HU treatment groups showed significant difference(84.2% vs. 52.4%；87.5% vs. 50.0%, P<0.05). ORR(82.4% vs. 78.9%) and 5-year PFS rate(58.8% vs. 57.9%） between IFN-α and HU treatment groups of ET patients without JAK2V617F mutations had no significant difference(P>0.05). The thromboembolic events, splenomegaly, bone marrow fibrosis of IFN-α treatment group were lower than those of HU treatment group; while hematologic adverse reactions of HU treatment group(Grade 1-2) was more than that of IFN-α treatment group (P<0.05). Conclusion ET and PV patients with JAK2V617F mutations who were treated with IFN-α could get a favorable progressionfree survival, and PV patients with JAK2V617F mutations could get rid of phlebotomy.