Objective To analyze the clinical significance of lymph node metastasis-related indexes in evaluating the prognosis of initially treated stage N2b colorectal cancer. Methods Two hundred and six patients with initially treated stage N2b colorectal cancer in Shenzhen People′s Hospital from January 2009 to November 2013 were retrospectively analyzed. All patients underwent radical resection of colorectal cancer. The correlation between lymph node metastasis-related indexes and postoperative 5-year overall survival rate was analyzed, including number of negative lymph nodes, number of positive lymph nodes, lymph nodes ratio (LNR), log odds of positive lymph nodes (LODDS). Results The postoperative 5-year overall survival rate was 54.4% (112/206), and the postoperative 5-year recurrence-free survival rate was 48.1% (99/206). Univariate analysis result showed that angioma thrombus or nerve invasion, T stage, postoperative adjuvant therapy, number of positive lymph nodes, number of negative lymph nodes, LNR and LODDS were significantly correlated with the postoperative 5-year overall survival rate (P＜0.01 or ＜0.05). Multivariate analysis result showed that number of negative lymph nodes, number of positive lymph nodes, LNR and LODDS were independent risk factors of postoperative the 5-year overall survival rate ( RR=2.371, 2.295, 2.758 and 2.671; 95% CI 1.598 to 3.485, 1.556 to 3.360, 1.880 to 4.058 and 1.814 to 3.915; P＜0.01). The areas under curve of negative lymph nodes, number of positive lymph nodes LNR and LODDS in predicting postoperative the 5-year overall survival rate were 0.668, 0.657, 0.692 and 0.684, and there was no statistical difference (P＞0.05). Conclusions The number of negative lymph nodes, number of positive lymph nodes, LNR and LODDS in initially treated stage N2b colorectal cancer patients are independent prognostic factors.