Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. In the present study, bioinformatics tools were systematically used to investigate the potential upstream effector involved in the progression of ccRCC. Using the Gene Expression Omnibus database and Library of Integrated Network-based Cellular Signatures L1000 platform, it was identified that GA-binding protein subunit β1 (GABPB1) was a potential effector gene. GABPB1 is a transcription factor subunit and its function in ccRCC is unclear. Elevated expression of GABPB1 mRNA in ccRCC was also observed in other clinical datasets from the Oncomine database. Following reverse transcription-quantitative polymerase chain reaction and western blot analysis, the ccRCC 786-O and A498 cell lines showed higher expression levels of GABPB1 than HK-2, a normal kidney cell line. Knockdown of GABPB1 in the 786-O and A498 cells significantly decreased the ability to form colonies by inducing the expression of p21Waf/Cip1. SurvExpress database analysis indicated that a higher expression of GABPB1 was associated with poor survival outcome in patients with renal cancer. These findings imply that GABPB1 serves an important role in the progression of ccRCC.