OBJECTIVE: The aim of this study was to systematically evaluate the efficacy and safety of the combination of dendritic cells and cytokine-induced killer cells (DC-CIK) adjuvant immunotherapy and chemotherapy in the treatment of multiple myeloma (MM). METHODS: Clinical trials were gathered by searching Web of Science, PubMed, Embase, Cochrane Library, Wanfang, and CNKI database. Outcome measurements including therapeutic efficacy, prognosis, immune function, and adverse events were extracted and evaluated. RESULTS: A total of 12 trials including 594 MM patients were involved in this study for statistical analysis. Results indicated that compared to chemotherapy alone, the combination of DC-CIK immunotherapy with chemotherapy significantly improved patients' overall response rate (ORR, odds ratio [OR] =2.77, 95% confidence interval [CI] =1.88-4.10, <0.00001), disease control rate (DCR, OR =2.90, CI =1.72-4.90, <0.0001), and life quality (<0.00001). The combined therapy showed advantages over chemotherapy alone in prognostic indicators including percentage of tumor cells (=0.04), serum levels of β2-microglobin (<0.0001), M protein (<0.00001), and creatinine (<0.0001), and 24 h urine light chains (<0.00001). After combined treatment, CD4 lymphocyte subsets' percentages, CD4/CD8 ratio, and cytokines levels of AgNOR, IFN-γ, IL-2, and IL-12 were significantly increased (<0.05), whereas CD8 and CD4CD25 percentages and IL-4, IL-6, IL-10, and TGF-β levels were obviously decreased (<0.01), indicating a recovered immune condition. CONCLUSION: Adjuvant DC-CIK immunotherapy enhances the efficacy of chemotherapy for MM and improves prognosis probably by reconstructing immune function.