This study was aimed to evaluate the prognostic value of serum IL-6 (sIL-6) in patients with multiple myeloma (MM). The sIL-6 level in 288 patients with MM was retrospectively analyzed, and the clinical characteristics and prognosis in patients with different IL-6 level were compared. The newly diagnosed patients with MM were divided into two groups: the low sIL-6 group (sIL-6 < 100 pg/ml) and the high sIL-6 group (sIL-6 ≥ 100 pg/ml). The results showed that high sIL-6 level was more common in patients with ECOG score>3, myeloma bone disease (MBD) between grade 2 to 4, and high creatinine level. There was no significant differences in age, abnormal karyotype percentage, chromosome 13q14 abnormality percentage, CD138(+)/CD38(+) cells percentage and the level of calcium, phosphorus, albumin, C-reactive protein, β2-MG, lactate dehydrogenase, hemoglobin, platelet between the two groups at diagnosis, and also no significant difference in response to initial induction chemotherapy among the two groups. The overall survival was significantly different between the low and high IL-6 groups (P = 0.04, 35 m vs 29 m), but no difference in time to progress between the two groups (P = 1.93, 23 m vs 14 m). It is concluded that the sIL-6 level correlates with the clinical characteristics and prognosis. Radioimmunoassay is an appropriate measurement for human IL-6 in serum, and suitable for clinical application.