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Circular RNA (circRNA), a member of non-coding RNA, plays an essential regulatory role in many human physiological and pathological processes; however, its role in clear cell renal cell carcinoma (ccRCC) still unclear. This study aims to investigate the effect and mechanisms of circRNA on ccRCC progression. A human circRNA microarray was used to discover differential expression circRNA, and a quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression of circRNA. The function and mechanism of circRNA were explored by cell transfection, cell counting kit-8, fluorescein isothiocyanate (FITC) Annexin V apoptosis detection, wound healing, transwell, and western blot. The result indicated that circ-APBB1IP was significantly up-regulated in ccRCC. In vitro, knockdown of circ-APBB1IP by siRNA suppressed the proliferation, migration, and invasion and increased the apoptosis of ccRCC cells. Further study found that knockdown of circ-APBB1IP up-regulated protein expression of cleaved caspase-3, cleaved caspase-7, cleaved caspase-8, cleaved caspase-9, Bax, Bad, Bak, E-cadherin and down-regulated expression of Bcl-2, N-cadherin, MMP-2, MMP-9, p-ERK1/2. Our result indicates that circ-APBB1IP has a vital function in ccRCC tumorigenesis. These findings suggest that circ-APBB1IP represents a novel potential biomarker and therapeutic target of ccRCC.