Colon cancer is the third most common cancer diagnosed in both men and women worldwide and one of the leading causes of cancer-related deaths. Based on where the cancer stared, we focused on the left-sided colon cancer and right-sided colon cancer in this study to reveal their pathological characteristics and their relationship to the KRAS gene mutation. From examining a total of 198 colorectal cancer specimens collected during 2013 and 2016 in Nan fang Hospital, we noticed that whether the cancer developed in left side or right side of the colon are highly relevant to the patients gender, age, tumor size, differentiation and distant metastasis. We found that right-sided colon cancers (RCC) are more likely to occur in women, be greater than 5 cm, and occur in patients older than 60 years, while left-sided colon cancers (LCC) are more prevalent in patients with poorly differentiated tumors and tumors with distant metastases. We then randomly selected 113 of the 198 samples and performed Sanger sequencing to examine their KRAS gene mutation. The result indicates that KRAS mutation is prominently higher in RCC compare to LCC, especially the mutation on the 12th codon GGT> GAT (G12D). In addition to the location in which the cancer developed, the KRAS mutation was also closely associated with the tumor size, degree of tumor differentiation, and lymph node metastasis. There was a significantly higher incidence of KRAS mutation in cases with RCC, poorly differentiated tumors, and non-lymph node metastasis compared to LCC with well-or moderately differentiated tumors with lymph node metastasis. Taken together, we determined that there are distinct differences in the clinicopathological characteristics of right-versus left-sided colon cancers and their correlation with the KRAS mutation. These differences suggest that practitioners need to diagnose and treat RCC and LCC differently.