【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.