There is a cellular crosstalk between Wnt/β-catenin and Hippo/Yes-related protein 1 signaling paths in colon cancer (CC) which promotes EMT processes that mediate the metastatic progression of CC. We aimed to evaluate follistatin-like 3 (FSTL3), ADAM12, and FAT4 expressions in CC. A statistical analysis was done to establish how disease-free survival, overall survival (OS), and relapse all performed a prognostic role. High FSTL3 was detected in 68% of CC and significantly related to left-sided tumors (P = 0.002) and the advanced tumor features, such as metastasis (P = 0.010), pT (P = 0.006), high grade (P = 0.005), lymph node contribution (P = 0.013), and advanced stage (P = 0.003). Positive ADAM12 expression was observed in 60% and significantly related to left-sided tumors (P = 0.001) and significantly common in high grade (P = 0.028), lymph node involvement (P < 0.001), and advanced stage (P = 0.004). Low FAT4 expression was recognized in 76% and linked with the right-sided tumors (P = 0.036). FAT4 expression was contrariwise linked with CC grade (P < 0.001). Furthermore, FAT4 expression was inversely correlated with lymph node involvement (P = 0.002), metastasis (P = 0.046), and advanced stage (P = 0.002). During the follow-up, 14 cases were relapsed and positively associated with high FSTL3 expression (P = 0.001) and ADAM12 expression (P < 0.001), but negatively linked with FAT4 expression (P = 0.003). Shorter disease-free survival was substantially correlated with positive ADAM12, extreme FSTL3, and low FAT4 expression (P < 0.001, P = 0.002, P = 0.003, consecutively). Moreover, Kaplan-Meier curves demonstrated a significant correlation between shorter OS with extreme FSTL3, positive ADAM12, and low FAT4 (P = 0.004, <0.001, 0.019, consecutively). High FSTL3, positive ADAM12, and low FAT4 expression are unfavorable prognostic influences in CC that may be accountable for relapse and therapeutic resistance in CC