Background and aim Several aspects of the correlation between colon cancer and hemostatic markers are still unknown to many researchers in the field. In this study, we evaluated the association, if any, of preoperative platelet (PLT) counts and plasma fibrinogen levels with postoperative lymph node involvement and venous invasion in colon cancer patients. Methods This study retrospectively included eighty patients with colon cancer (mean age 58.09 years; 37% female 63% male). Results Patients with negative lymph nodes and venous invasion showed a significantly lower PLT count and higher fibrinogen level than their counterparts, i.e., patients with positive lymph nodes (p<0.001, all of them) and venous invasion (p<0.001, all of them). The results also showed a positive association of PLT counts and fibrinogen levels with lymphatic invasion (r=0.670, pr=0.639, p<0.001, respectively) and a positive association of PLT counts and fibrinogen levels with venous invasion (r=0.3988, pr=0.5268, p<0.001, respectively). According to the results of the ROC curve analysis, when the PLT count cutoff was 290/mm(3), the sensitivity and specificity were 82% and 86.67%, respectively (AUC = 0.8840, p<0.0001, 95% CI 0.8084-0.9596). When the fibrinogen level cutoff was 310.0 mg/dL, the sensitivity and specificity were 72% and 96.67%, respectively (AUC 0.8790, p <0.0001, 95% CI 0.8067-0.9513). Conclusion The preoperative PLT count and plasma fibrinogen level may be considered key markers to monitor postoperative lymph node involvement and venous invasion in colon cancer patients.