Objective:To investigate the expression of miRNA-21 in serum of patients with multiple myeloma (MM) and its significance.Methods:The data of 55 MM patients and 20 healthy controls in the Second Hospital of Hebei Medical University from July 2019 to June 2020 were retrospectively analyzed. Among the MM patients, 20 cases were diagnosed without treatment, 15 cases were in complete remission (CR), and 20 cases were clinically relapsed. Blood samples were collected from all subjects, and the relative expression levels of miRNA-21 were detected by real-time quantitative polymerase chain reaction (qRT-PCR), and the correlation of miRNA-21 expression with β 2-macroglobulin (β 2-MG), creatinine, hemoglobin, albumin, t(4;14) mutation, 13q14 mutation and prognosis were analyzed. The MM cell line LP-1 was selected, and normal bone marrow CD138-positive plasma cells were sorted by immunomagnetic beads as control cells. The relative expression levels of miRNA-21 in the two groups of cells were detected by qRT-PCR. Results:The serum relative expression level of miRNA-21 in MM group was higher than that in healthy control group (1.50±0.10 vs. 1.03±0.06, t = 7.04, P = 0.002). The serum expressions of miRNA-21 in newly diagnosed untreated MM patients and relapsed/refractory MM patients were high (1.50±0.10 and 3.13±0.32), and compared with the healthy control group, the differences were statistically significant ( t values were 7.04 and 10.22, both P < 0.05). The relative expression level of miRNA-21 in MM patients with complete remission (CR) was 1.27±0.25, which had no significant difference compared with the healthy control group ( t = 1.76, P = 0.152). The serum expression level of miRNA-21 in MM patients with high β 2-MG, high creatinine, low hemoglobin, low albumin, t(4;14) mutation, 13q14 mutation, non-remission and recurrence was significantly increased (all P < 0.05). The relative expression level of miRNA-21 in LP-1 cell line was higher than that in control cells (1.56±0.05 vs. 1.00±0.06), and the difference was statistically significant ( t = 11.73, P < 0.01). Conclusions:The miRNA-21 may be a molecular marker to assist in the diagnosis and efficacy evaluation of MM.