Colon cancer is one of the most common malignant tumors worldwide, and the molecular mechanisms involved in the oncogenesis and progression of colon cancer remain unclear. Early growth response 1 (Egr-1) is a transcription factor that is closely associated with several tumor processes; however, its role in colon cancer is unknown. The present study aimed to explore the function and mechanism of transcription factor Egr-1 in colon cancer progression. The association between Egr-1 expression and the survival of patients with colon cancer was analyzed. Transwell assay was used to measure the migration and invasion of colon cancer cells. Cell Counting Kit-8 assay was used to evaluate the cell proliferative ability. Reverse transcription-quantitative PCR and western blot assays were used to identify whether Egr-1 could regulate cyclin-dependent kinase-like 1 (CDKL1). Luciferase and chromatin immunoprecipitation assays were used to detect the mechanism by which Egr-1 regulated CDKL1. Based on The Cancer Genome Atlas database, it was found that low Egr-1 expression was associated with a poor prognosis in patients with colon cancer. Furthermore, overexpression of Egr-1 inhibited colon cancer cell proliferation, migration, and invasion, whereas knockdown of Egr-1 increased colon cancer cell proliferation, migration and invasion. Additionally, overexpression of Egr-1-induced cell proliferation, migration and invasion were reversed by overexpression of CDKL1. Furthermore, it was demonstrated that Egr-1 regulated CDKL1 expression at the transcriptional level. The present study illustrated the mechanism of Egr-1 regulating CDKL1, by which Egr-1 affected colon cancer cell proliferation, migration and invasion. The current findings suggested that Egr-1/CDKL1 may be a new promising target for the treatment of colon cancer.