〔Abstract〕 Objective To investigate the value of methyltransferase-like protein 16(METTL16) in the clinical diagnosis and prognostic prediction of multiple myeloma(MM) patients. Methods The expression level and prognostic potential of each gene involved in N6-methyladenosine(m6A) modification in MM were respectively analyzed in the databases of the Multiple Myeloma Research Foundation(MMRF) and the Genotype-Tissue Expression Project(GTEx). Bone marrow specimens from 26 patients with initial diagnosis of MM and 19 patients with MM after treatment with standard regimens and peripheral blood specimens from 24 normal subjects were collected respectively, and the expression levels of m6A genes were determined by qRT-PCR. The correlation between METTL16 expression and various laboratory and clinical indexes was analyzed: hemoglobin(Hb), white blood cell count(WBC), platelet count(PLT), blood creatinine(Scr), serum calcium(Ca2+), β-microglobulin(β-MG), bone destruction, ISS stage, type, and overall survival(OS) in the patients with primary diagnosis. The expression levels of interleukin(IL)-4, IL-6, IL-10, IL-18 and chemokine ligand 2(CCL2), CCL3, CCL4 in the specimens were further examined and their correlation with the expression of METTL16 was investigated. Results Database analysis suggested that METTL16 expression was significantly higher in MM patient samples compared with normal controls, which was associated with poor prognosis and had certain diagnostic value. qRT-PCR results showed that the expression level of METTL16 in the bone marrow of patients with initial diagnosis of MM was significantly higher than that of treated patients and normal controls. Its expression was positively correlated with hemoglobin, leukocytes and stage, and its expression was positively correlated with CCL4 expression. Conclusion METTL16 expression was significantly elevated in patients with MM, and its expression level was correlated with anemia, more bone destruction and worse stage, which might indicate a poor prognosis. The significant correlation between the expression of METTL16 and CCL4 suggests that METTL16 may play a corresponding pathogenic role through the relevant pathway. METTL16 will have significant clinical value in the management of MM.