Colon cancer is one of the most common malignancies causing the majority of cancer-related deaths. Gelsolin (GSN) has been found to be dysregulated in various cancers. However, the secreted GSN in colon cancer remains largely unknown. In the present study, we explored the expression profile of GSN in colon cancer tissues and the diagnostic value of serum GSN in colon cancer. In addition, the effects of secreted GSN in colon cancer cells were studied. We thus found that immunoreactive GSN levels were significantly lower in colon cancer tissues than those in non-tumor colon tissues. Functional studies demonstrated that secreted GSN could restrain cell invasion and migration in vitro. Mechanistically, dose dependent recombinant GSN down-regulated the expression of MMP2 and MMP9, which might restrain the process of cell invasion and migration. Furthermore, serum levels of GSN were significantly lower in colon cancer patients than those in healthy volunteers, and ROC curves showed serum level of GSN had a better diagnostic value for colon cancer (AUC=0.932) than the traditional tumor biomarker Carcinoembryonic Antigen (CEA) or Carbohydrate Antigen 19-9 (CA199). In conclusion, our results suggest that the secreted GSN restrains the invasion and migration of colon cancer cells. Meanwhile, the serum GSN may be a new biomarker for the diagnosis of colon cancer.