AT-rich interactive domain 1A (ARID1A) is a key member of the SWI/SNF chromatin-modeling complex, and the gene has emerged as a tumor suppressor in various human cancers. In the present study, we investigated the expression pattern of ARID1A in human colorectal carcinoma. We found that ARID1A expression was decreased in colorectal carcinoma compared with normal tissue. Loss of ARID1A significantly correlated with poor differentiation (p = 0.0009). We also explored the involvement of ARID1A in the biological behavior of colorectal cancer cell lines. ARID1A overexpression by plasmid transfection in SW620 cell line inhibited proliferation and facilitated 5-fluorouracil-induced apoptosis. ARID1A depletion by siRNA in SW480 cell line promoted proliferation ability and inhibited 5-fluorouracil-induced apoptosis. Furthermore, we found that ARID1A regulated the activity of Akt signaling pathway. In conclusion, our data suggested that ARID1A serves as an important tumor suppressor in colorectal carcinoma and regulates proliferation and chemoresistance of colorectal cancer cells.