Accumulating evidence has demonstrated that thioredoxin interacting protein (TXNIP) is abnormally expressed in a variety of malignant tumors and functions as a tumor suppressor. However, the association between TXNIP and clear cell renal cell carcinoma (CCRCC) has not yet been fully elucidated. The aim of the present study was to evaluate the role of TXNIP in CCRCC using The Cancer Genome Atlas (TCGA) database. The RNA sequencing data and corresponding clinical data were collected from TCGA database. The association between TXNIP and patient clinicopathological characteristics was analyzed using analysis of variance and logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess the association between TXNIP and overall survival. Gene Set Enrichment Analysis (GSEA) was used to explore the associated signaling pathways. TXNIP expression was identified to be decreased in CCRCC tissues compared with normal tissues. The decreased expression of TXNIP in CCRCC was significantly associated with clinical stage [OR=0.509 for III vs. I (P=0.002); OR=0.527 for IV vs. I (P=0.012)], T stage [OR=0.552 for T3 vs. T1 (P=0.002)] and grade [OR=0.261 for G4 vs. G1 (P=0.027)]. Kaplan-Meier survival analysis indicated that cases of CCRCC with low TXNIP expression were associated with poorer prognoses compared with those with a high expression level (P=0.002). Univariate and multivariate Cox analyses indicated that TXNIP was an independent prognostic factor in CCRCC. GSEA revealed that 6 pathways exhibited significant differential enrichment in the TXNIP high-expression phenotype, including the WNT signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the phosphatidylinositol signaling system, the transforming growth factor-ß (TGF-ß) signaling pathway, autophagy and the Janus kinase (JAK)-STAT signaling pathway. Taken together, the results of the present study indicate that TXNIP expression may be a potential prognostic marker for patients with CCRCC. In addition, the WNT signaling pathway, MAPK signaling pathway, phosphatidylinositol signaling system, TGF-ß signaling pathway, autophagy and the JAK-STAT signaling pathway may be the crucial pathways regulated by TXNIP in CCRCC.