Abstract: Objective To evaluate the effectiveness of bortezomib-based chemotherapy in the treatment of monoclonal gammopathy of renal significance (MGRS). Methods A total of 37 patients who were diagnosed with MGRS in the Affiliated Hospital of Xuzhou Medical University from May 2015 to December 2020 were enrolled. According to their chemotherapy regimen, they were divided into two groups: a bortezomib group (n=18) and a non-bortezomib group (n=19). Both groups were compared for the corresponding effectiveness after different treatment periods. Results After six treatment periods, the blood creatinine and 24-hour urine protein level remarkably decreased but serum albumin level increased in the bortezomib group, compared with the non-bortezomib group (P＜0.05); After three and six treatment periods, the remission rate of proteinuria in the bortezomib group was significantly higher than that in the non-bortezomib group (P＜0.05). Compared with those before treatment, both groups presented statistical difference in the detection rate of monoclonal immunoglobulin(MIg) through serum protein electrophoresis and serum immunofixation electrophoresis as well as the levels of serum free light chain, blood total light chain and urine total light chain after treatment (P<0.05). Conclusions Bortezomib-based chemotherapy can reduce the levels of blood creatinine and urine protein in MGRS patients, and reduce the production of MIg.