Objective To study the regulation to colon cancer cellular biological properties through miR-18a targeting ataxia-telangiectasia mutated gene (ATM). Methods A target of miR-18a was predicted by using bioinformatics tools. The miR-18a mimics and inhibitors were designed and synthesized. The expression of endogenous miR-18a in colon cancer cell line HCT116 was up-regulated or down-regulated by transfection. The effect of overexpression of miR-18a on cellular proliferation, invasion and migration via regulation of ATM gene expression was confirmed in vitro by using qRT-PCR, Western blot, MTT assay, clone forming assay and Transwell method, respectively. Results ATM was identified as a potential target gene of miR-18a in the bioinformatics analysis. In addition, through transient transfection leading to the overexpression of miR-18a in HCT116 cell, the expression level of ATM was decreased. Down-regulation of HCT116 cell proliferation activity while significantly reducing HCT116 cell clone forming ability, lateral migration ability and longitudinal invasion ability were observed after transfected with miR-18a mimics. All of the changes were related to the overexpression of miR-18a. Conclusion miR-18a inhibited the proliferation and migration of colon cance cell HCT116 through negative regulation of ATM expression.