Objective The aim of the study was to assess the quality of life (QoL) of patients with esophageal cancer, and to explore the main socioeconomic factors that affect the QoL. Method A multicenter cross-sectional study design was used. Data were collected using scales including the interviewer-administered general situation questionnaire designed by the authors, the Quality of Life Questionnaire-core 30 Version 3 in Chinese (QLQ-C30), and the Patientgenerated Subjective Global Assessment (PG-SGA) from a nationwide survey conducted previously in China. The role of each covariate in the full model was assessed using the QoL as the primary outcome in a multilevel ordinal logistic regression analysis. Results In total, 1223 patients were included, among whom 1009 (82.5%) were males, and 504 (41.2%) were older than 65 years old. The findings indicate that patients with esophageal cancer in China face a poor quality of life with a mean global quality of life scored of 58.33 (66.67). The most significant factors influencing quality of life were the nutritional support, PG-SGA scores and level of education. Compared with patients who had a PG-SGA score ≥ 9, patients with scores between 0-1 had significantly better scores in five scales: the PF (physical functioning), RF (role functioning), CF (cognitive functioning), EF (emotional functioning) and SF (social functioning) (OR: 4.75, 4.84, 2.12, 2.81, and 3.00). Conclusion Nutritional support and PG-SGA scores significantly influenced the quality of life of patients with esophageal cancer. It appears that most patients with esophageal cancer are in urgent need of symptom alleviation and/or concurrent intervention.