Previous studies have shown a significant increase in monoclonal gammopathy (MG) prevalence in patients with human immunodeficiency virus (HIV). HIV and MG both can cause renal injury and have attracted increasing nephrologists' attention. To date, there has been a lack of relevant studies on the renal pathology of HIV combined with MG. Here, we report a case of a newly diagnosed HIV patient with co-morbid MG and subsequent or concurrent massive proteinuria whose renal biopsy showed minimal change disease (MCD). After a period of administration of highly active antiretroviral therapy (HAART), HIV viral RNA was undetectable in plasma, along with complete remission of the nephropathy. However, there was no significant effect on MG.