Objective To evaluate the efficacy and safety of lenalidomide(Len)-based regimens in the treatment to patients with multiple myeloma (MM). Methods Twenty-five multiple myeloma patients who received Len-based regimens were enrolled in this study. There were 5 newly-diagnosed MM patients, 13 relapsed/refractory (rel/ref) MM and 7 MM patients at plateau after treatment. The newly-diagnosed patients received R-PAD regimen, rel/ref MM received R-MD and the patients at plateau(maintenance treatment group) due to more than 2 grade peripheral neuropathy (PN) received Len monotherapy. Results All of the five newly-diagnosed MM achieved complete remission (CR) (100 %) after 2 courses of theatment; of 13 rel/ref patients (76.92 %) achieved overall response, including 3 (23.08 %) achieving CR, 2 (15.38 %) very good partial response (VGPR), 5 (38.46 %) partial response (PR) and the overall response rate was 76.92 %. Two of the other three no response patients had stable disease(SD) and one had progress disease(PO). The seven patients in maintenant treatment group maintained remission in an average follow-up period of 38 weeks and their PN was relieved in various degrees. Conclusion R-PAD regimen is a highly active regimen for newlydiagnosed MM and R-MD regimen is a promising regimen for rel/ref MM, especially for the patients with serious PN; Len may be a good choice as maintenant chemotherapy for the patients with PN.