Objective To explore the correlations of lymph node metastasis with clinicopathological factors and tumor markers (TM) in colorectal cancer, and to look for the risk factors for lymphatic metastasis. Methods The complete clinicopathological data and TM data of 499 patients with colorectal cancer who underwent radical resection in the First Affiliated Hospital of Guangxi Medical University from 2012 to 2014 were retrospectively analyzed. The correlations of lymphatic metastasis with clinicopathological factors and TM were evaluated by single-factor analysis and multivariate logistic regression analysis. Results The results of single-factor analysis indicated that there was no significant correlation between lymphatic metastasis and patients’ age, gender, tumor location, tumor type, perineural invasiveness, or preoperative CA153 level (P > 0.05). The preoperative levels of CEA, CA724, CA199, CA242 and CA125 were significantly correlated with lymph metastasis (P < 0.05). Logistic regression analysis showed that the depth of invasion, carcinoma vascular tumor emboli, tumor histological types and CA242 were the independent risk factors for lymphatic metastasis (P < 0.05). Conclusions The depth of cancer invasion, carcinoma vascular tumor emboli, tumor histological types and CA242 are the independent risk factors for lymph node metastasis. Preoperative detection of CEA, CA724, CA199 and CA125 has certain reference value in the diagnose of lymph node metastasis in colorectal cancer.