Background: Interleukin-10 (IL-10) is a inhibiting inflammatory cytokine that plays an important role in immune suppressive microenvironment in multiple myeloma (MM). Whether the level of serum IL-10 could predict treatment response and survival outcomes or not needs to be investigated in MM patients. Methods: The level of IL-10 in serum was measured using enzyme-linked immunosorbent assay in 188 patients with newly diagnosed MM. Results: The best cutoff value for IL-10 in predicting survival is 169.69 pg ml(-1) with an area under the curve (AUC) value of 0.747 (P < 0.001). In all, 92 patients (48.9%) were classified as high-IL-10 group (> 169.96 pg ml(-1)) and 96 patients (51.1%) as low-IL-10 group (<= 169.96 pg ml(-1)). The overall response rate (ORR) was 79.2% in low-IL-10 group, significantly higher than that in high-IL-10 group (53.3%, P < 0.001). Patients in low-IL-10 group had significantly better survival compared with those in high-IL-10 group (3-year PFS rate: 69.3% vs 13.3%, P < 0.001; 3-year OS rate: 93.6% vs 51.9%, P < 0.001). Multivariate analysis revealed that serum IL-10 level > 169.96 pg ml(-1) at diagnosis and certain cytogenetic abnormalities were two adverse factors for PFS and OS. Conclusions: Our data suggest that serum IL-10 at diagnosis is a novel, powerful predictor of prognosis for MM.