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Clear cell renal cell carcinoma (ccRCC) is the most common and lethal renal malignant tumor in adults. The aim of the present study was to identify the key genes involved in ccRCC metastasis. Expression profiling data for ccRCC patients with metastasis and without metastasis were obtained from The Cancer Genome Atlas database. The datasets were used to identify differentially expressed genes (DEGs) between the metastasis group and the non-metastasis group using the DESeq2 package. Function enrichment analyses of DEGs were performed. The protein-protein interaction (PPI) network was constructed and analyzed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape for further analysis of the identified hub genes. A total of 472 DEGs were identified, including 247 that were upregulated and 225 that were downregulated in the metastasis group. Gene Ontology enrichment analysis revealed that DEGs were mainly enriched in cell transmembrane movement and mitotic cell cycle process. Kyoto Encyclopedia of Genes Genomes pathway analysis revealed that the DEGs were mainly involved in the 'cell cycle' (hsa04110), 'collecting duct acid secretion' (hsa04966), 'complement and coagulation cascades' (hsa04610) and 'aldosterone-regulated sodium reabsorption' (hsa04960) pathways. Using the PPI network, 35 hub genes were identified, and the majority of them were upregulated in ccRCC tissue compared with normal kidney tissue. The expression levels of certain hub genes (CDKN3, TPX2, BUB1B, CDCA8, UBE2C, NDC80, RRM2, NCAPG, NCAPH, PTTG1, FAM64A, ANLN, KIF4A, CEP55, CENPF, KIF20A, ASPM and HJURP) were significantly associated with overall survival and recurrence-free survival in ccRCC. The present study has identified key genes associated with the metastasis of ccRCC.