Circular RNAs (circRNAs) exhibit essential regulation in the malignant development of clear cell renal cell carcinoma (ccRCC). The aims of this study were to investigate the role and mechanism of circ_0003146 in the biologic behaviors of ccRCC. RNA level analysis was performed through reverse transcription-quantitative PCR assay. Cell proliferation was measured by EdU assay and cell counting kit-8 assay. The protein expression was analyzed using a western blot. Flow cytometry and caspase 3 activity assay were used to assess cell apoptosis. Cell migration and invasion were evaluated via wound healing assay and transwell assay. Circ_0003146 function in vivo was determined by xenograft tumor assay. Dual-luciferase reporter assay was applied for target relation analysis. Circ_0003146 upregulation was detected in ccRCC tissues and cells. Downregulation of circ_0003146 induced inhibition of proliferation, migration, invasion and EMT but the promotion of apoptosis in ccRCC cells. Tumor growth in vivo was inhibited after knockdown of circ_0003146. Circ_0003146 directly interacted with miR-1272, and the miR-1272 sponging effect was responsible for the function of circ_0003146. Scavenger receptor class B type 1 (SCARB1) was a target of miR-1272, and circ_0003146 regulated SCARB1 level by absorbing miR-1272. The regulation of circ_0003146 in ccRCC progression was achieved by upregulating SCARB1 in part. The current findings demonstrated that circ_0003146 contributed to the malignant progression of ccRCC via inducing SCARB1 upregulation by targeting miR-1272.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.