Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of kidney cancer in adults, accompanied by an increasing incidence rate worldwide. We found that SBF2-AS1 was a differentially expressed long-noncoding RNA (lncRNA) in ccRCC through the microarray-based expression analyses. The aim of the present study was to explore the role of SBF2-AS1 in ccRCC development by assessing its effects on cellular processes and further investigate the underlying mechanism. SBF2-AS1 was found to be highly expressed in ccRCC tissues and cells. Ectopic expression and knockdown of SBF2-AS1 and miR-338-3p were performed in ccRCC 768-O cells to explore their effects on cell proliferation, migration, invasion, apoptosis and autophagy by EdU assay, scratch test, Transwell assay, calcein-AM/PI, and GFP-LC3 immunofluorescence assays, respectively. The interactions among SBF2-AS1, miR-338-3p and ETS1 were analyzed using dual-luciferase reporter, RIP and RNA pull-down assays. SBF2-AS1 specifically bound to miR-338-3p and inhibited its expression. Moreover, ETS1 was targeted by miR-338-3p. The knockdown of SBF2-AS1 or ETS1 or overexpression of miR-338-3p resulted in reduced cell proliferation, migration and invasion but elevated cell apoptosis and autophagy. In vivo experiments verified the tumor-suppressive role of silencing SBF2-AS1 in tumor growth of nude mice xenografted with ccRCC cells. Thus, silencing SBF2-AS1 exerted suppressive effects on ccRCC by elevating miR-338-3p and suppressing ETS1.