ObjectiveThe aim of this study was to establish a nurse-led supportive care program based on telephone and Internet support and evaluate its efficacy in comparison with conventional care on enhanced recovery after surgery. MethodsThe study was designed as an open-label, randomized controlled trial to value the efficacy of a nurse-led supportive care program in comparison with conventional care. A convenience sampling method was employed to recruit patients with esophageal cancer in a tertiary Grade A cancer center in Beijing from November 2018 to January 2019. Patients were assigned randomly (1:1) to one of the two groups (intervention group vs control group) via a web randomization system. The control group received conventional care. Patients from the intervention group received conventional care and one-on-one phone calls from nurses following their discharge assessments and education about nutrition and symptoms. Nurses also set up a WeChat group, which they invited patients to join in before discharge for better communication during follow-up. Statistical testing, including nutritional status, quality of life, the helpfulness of the follow-up service, and the patients’ satisfaction with their care, was conducted 6 months after discharge to assess for differences between the two groups. The independent sample t, chi-squared, and Mann–Whitney tests were used to compare between the experiences of the intervention and control groups. The Spearman correlation analysis was used for the analysis of correlation of the nutritional index and quality of life. ResultsFinally, 168 patients were included in the study, with 86 patients in the intervention group and 82 in the control group. Significant differences between the intervention and control groups were found in the nutrition risk screening 2002 and simple diet self-assessment tool scores. The changes in blood albumin, prealbumin, and transferrin were also statistically significant. All (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) QLQ-C30 results of the intervention group were better than those of the control group. A significant positive correlation of the simple diet self-assessment tool (the higher, the better) and the scores for total health/quality of life were detected (r = 0.214, P = 0.005). A significant negative correlation of the nutrition risk screening 2002 (the lower, the better) and the scores of total health/quality of life was detected (r = −0.446, P = 0.000). The patients’ scores on the helpfulness of the follow-up service and their satisfaction with it were both significantly higher in the intervention group than in the control group. ConclusionsThis study highlighted the important role of nurse-led supportive care based on telephone and Internet-based support for patients after enhanced recovery after surgery. The supportive care improved patients’ nutritional status, elevated their quality of life, and improved their satisfaction with the care provided to them.