Objective To analyze the risk factors of lymph node metastasis in patients with submucosal deep infiltration of superficial esophageal squamous cell carcinoma, and to build a scoring system to predict the risks for lymph node metastasis and evaluate its clinical application value. Methods Data of 267 patients with submucosal deep infiltration (SM≥200 μm) of superficial esophageal squamous cell carcinoma confirmed by pathology after surgery in the Affiliated Drum Tower Hospital of Nanjing University between 2005 and 2017 were analyzed retrospectively. Multivariate Logistic regression analysis was conducted to explore the independent risk factors of lymph node metastasis. Independent variables with P<0.1 were selected to establish a risk factor scoring system and the independent variables were scored. According to the cut-off point of receiver operating characteristic (ROC) curve, 267 cases were divided into different risk groups. The rate of lymph node metastasis was compared among different groups. Results Of the 267 cases, 71 (26.59%) had been pathologically confirmed lymph node metastasis after surgery. Multivariate Logistic regression analysis showed that moderate or low degree of differentiation (P=0.015, OR=2.802, 95%CI: 1.225-6.409), vascular invasion (P=0.043, OR=3.450, 95%CI: 1.040-11.445) and lymphatic invasion (P<0.001, OR=36.985, 95%CI: 13.699-99.856) were independent risk factors for lymph node metastasis. Abnormal mucosa muscular layer hyperplasia was not an independent risk factor for lymph node metastasis (P=0.081, OR=2.005, 95%CI: 0.918-4.380), but its P<0.1. According to the above four factors, the scoring system was established, and the factors of moderate or low degree of differentiation, abnormal mucosal muscle layer hyperplasia, vascular invasion and lymphatic invasion were assigned 1 point, 1 point, 2 points and 5 points respectively. ROC curve analysis showed that the best diagnostic cut-off point of lymph node metastasis was score>2, and 267 cases were divided into low-risk group (score 0-1, n=143), moderate-risk group (score 2-5, n=79) and high-risk group (score 6-9, n=45). There was significant difference in lymph node metastasis rate among the three groups (χ2=119.712, P<0.001), and trend Chi-Squared test showed that the lymph node metastasis rate of the three groups had a linear upward trend (χ2=109.298, P<0.001). Conclusion Moderate and low-grade differentiation, vascular invasion, and lymphatic invasion are independent risk factors for lymph node metastasis in submucosal deep infiltration of superficial esophageal squamous cell carcinoma. Furthermore, the risk assessment system of lymph node metastasis based on the above three factors combined with abnormal mucosa muscular layer hyperplasia has good clinical application value, which can guide individualized decision and has important significance for postoperative management.