The lack of early diagnostic markers and noveltherapeutic targets for clear cell renal cell carcinoma (ccRCC)negatively affects patient prognosis. Cancer metabolism isan attractive area for the understanding of the molecularmechanism of carcinogenesis. The present study attemptedto identify metabolic changes from the view of the expressionof metabolism-associated genes between control samples andthose of ccRCC at different disease stages. Data concerningccRCC gene expression obtained by RNA-sequencingwas obtained from The Cancer Genome Atlas and dataon metabolism-associated genes were extracted using theRecon2 model. Following analysis of differential geneexpression, multiple differentially expressed metabolic genesat each tumor‑node‑metastasis disease stage were identified,compared with control non-disease samples: Metabolicgenes (305) were differentially expressed in stage I disease,323 in stage II disease, 355 in stage III disease and 363in stage IV disease. Following enrichment analysis fordifferential metabolic genes, 22 metabolic pathways wereidentified to be dysregulated in multiple stages of ccRCC.Abnormalities in hormone, vitamin, glucose and lipidmetabolism were present in the early stages of the disease,with dysregulation to reactive oxygen species detoxifica-tion and amino acid metabolism pathways occurring withadvanced disease stages, particularly to valine, leucine, andisoleucine metabolism, which was substantially dysregulatedin stage IV disease. The xenobiotic metabolism pathway,associated with multiple cytochrome P450 family genes, wasdysregulated in each stage of the disease. This pathway isworthy of substantial attention since it may aid understandingof drug resistance in ccRCC. The results of the present studyoffer information to aid further research into early diagnosticbiomarkers and therapeutic targets of ccRCC.