Colon cancer, as one of the common malignant tumors, has the highest morbidity and mortality. We investigated the clinical significance and possible mechanism of the circular RNA circHIPK2 in the progression of colorectal cancer (CRC). Quantitative analysis of mRNAs, gene microarray hybridization, immunofluorescence, luciferase reporter assay, proliferation assay, EDU staining, subcellular location analysis and Western blotting. circHIPK2 expression was upregulated in patients with CRC compared with paracancerous tissues. In contrast, patients with high circHIPK2 expression had lower overall survival rate and disease-free survival rate than those with low circHIPK2 expression. circHIPK2 expression in normal intestinal epithelial cells was lower than that in CRC cell lines. circHIPK2 promoted CRC progression. miR-485-5p reduced CRC progression. miR-485-5p, as the target of circHIPK2 in CRC model, played a role in promoting CRC progression and expediting HSP90 ubiquitination. HSP90 ubiquitination by miR-485-5p can promote cell proliferation. circHIPK2 has potential clinical significance in CRC progression, which may serve as an exceptional candidate for further therapeutic exploration.