Circular RNAs (circRNAs) are emerging as pivotal modulators of cellular processes; however, their functions in colorectal cancer (CRC) are not fully understood. Circ_0043278 was identified as a downregulated circRNA in CRC patients by bioinformatics analysis of two patient cohorts. In addition, four predictive platforms were used to enrich miR-6508-3p as a putative microRNA (miRNA) target of circ_0043278. The interaction between circ_0043278 and miR-6508-3p was validated by dual-luciferase reporter assays, and their regulatory circuits were confirmed by RT-qPCR.