Background: Propofol is a commonly used intravenous anesthetic and has been found to perform anticancer effects in many cancers. However, the effects and mechanisms of propofol in clear cell renal cell carcinoma (ccRCC) remain largely undefined. Methods: The expression of circular RNA FBXW7 (circFBXW7) and miR-942 was detected by qRT-PCR. Cell proliferation, apoptosis, migration, and invasion capacities were analyzed using cell counting kit-8, colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the expression levels of PCNA, Cleaved-caspase 3 and MMP protein. The bindings between miR-942 and circFBXW7 were verified using RNA pull-down, dual-luciferase reporter, and RIP assays. Xeno-graft tumor analysis was employed to detect tumorigenesis in vivo. Results: Propofol alleviated cell proliferation, migration, invasion, and induced apoptosis in vitro and impeded tumor growth in vivo in ccRCC. Propofol elevated the level of circFBXW7, which knockdown reversed the anticancer effects of propofol on ccRCC cell tumorigenesis. CircFBXW7 directly bound to miR-942, and suppressed ccRCC cell malignant biological behaviors via targeting miR-942. Besides that, propofol decreased miR-942 expression, and miR-942 overexpression attenuated the effects of propofol on ccRCC cells. Moreover, propofol could regulate miR-942 expression through circFBXW7. Conclusion: Propofol suppressed the growth, migration, and invasion of ccRCC cells by regulating circFBXW7/miR-942 axis, suggesting a potential therapeutic strategy for the intervention of human ccRCC development.