The prognostic value of tumor size in colon cancer remains controversial. This study aimed to reveal the correlation between tumor size and prognosis of colon cancer. A total of 491 patients with colon cancer were included in this study. The correlation of tumor size with prognosis, mismatch repair status, and other clinicopathological characteristics as well as tumor microenvironment was analyzed. For stage IIA microsatellite stable (MSS) colon cancer, tumors sized <3.5cm and ≥5cm were associated with a poorer disease free survival (DFS) compared with tumors sized between 3.5 and 5cm (P = .002). Small tumor size (HR = 5.098, P = .001) and large tumor size (HR = 2.749, P = .029) were found to be independent prognostic factors for stage IIA MSS colon cancer. Moreover, high expression of transgelin (TAGLN), a marker of cancer-associated fibroblasts (CAFs), was found to be an independent prognostic factor for poorer DFS (HR = 9.651, P = .009), which was also associated with smaller tumor size (P = .027). Small (<3.5cm) and large (≥5cm) tumor sizes are associated with decreased DFS in stage IIA MSS colon cancer. Enrichment of TAGLN+ CAFs is associated with decreased DFS and small tumor size.