Plasma is generated by ionizing neutral gas molecules, resulting in a mixture of energy particles, including electrons and ions. Recent progress in the understanding of non-thermal atmospheric plasma has led to applications in biomedicine. However, the exact molecular mechanisms involved in plasma-induced cell growth arrest are unclear. In this study, we investigated the feasibility of non-thermal atmospheric plasma treatment for cancer therapy and examined the mechanism by which plasma induces anti-proliferative properties and cell death in human colorectal cancer cells. Non-thermal atmospheric plasma induced cell growth arrest and induced apoptosis. In addition, plasma reduced cell migration and invasion activities. As a result, we found that plasma treatment to the cells increases β-catenin phosphorylation, suggesting that β-catenin degradation plays a role at least in part in plasma-induced anti-proliferative activity. Therefore, non-thermal atmospheric plasma constitutes a new biologic tool with the potential for therapeutic applications that modulate cell signaling and function.