Multiple myeloma (MM) is a hematological malignancy in which monoclonal plasma cells multiply in the bone marrow and monoclonal immunoglobulins are overproduced in older people. Several molecular and cytogenetic advances allow scientists to identify several genetic and chromosomal abnormalities that cause the disease. The comprehension of the pathophysiology of MM requires an understanding of the characteristics of malignant clones and the changes in the bone marrow microenvironment. This study aims to identify the central genes and to determine the key signaling pathways in MM by in silico approaches. A list of 114 differentially expressed genes (DEGs) is important in the prognosis of MM. The DEGs are collected from scientific publications and databases ( https://www.ncbi.nlm.nih.gov/ ). These data are analyzed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software ( https://string-db.org/ ) through the construction of protein-protein interaction (PPI) networks and enrichment analysis of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, by CytoHubba, AutoAnnotate, Bingo Apps plugins in Cytoscape software ( https://cytoscape.org/ ) and by DAVID database ( https://david.ncifcrf.gov/ ). The analysis of the results shows that there are 7 core genes, including TP53; MYC; CDND1; IL6; UBA52; EZH2, and MDM2. These top genes appear to play a role in the promotion and progression of MM. According to functional enrichment analysis, these genes are mainly involved in the following signaling pathways: Epstein-Barr virus infection, microRNA pathway, PI3K-Akt signaling pathway, and p53 signaling pathway. Several crucial genes, including TP53, MYC, CDND1, IL6, UBA52, EZH2, and MDM2, are significantly correlated with MM, which may exert their role in the onset and evolution of MM.