Objective: To study the clinical effect of applying high-quality care in the care of patients with esophageal cancer. Methods: Ninety patients with esophageal cancer treated in our hospital from November 2016 to November 2019 were selected as experimental subjects, and the effects of each group were explored after digital parity grouping. The control group (45 cases): applied routine nursing; the experimental group (45 cases): applied high-quality nursing throughout the course. The nursing satisfaction, Self-Rating Depression Scale (SDS) score, Self-Rating Anxiety Scale (SAS) score, and incidence of postoperative adverse reactions were compared between the 2 groups. Results: The total satisfaction of nursing in the experimental group was 97.78% (44/45), which was higher than that in the control group (80.00%, 36/45). The comparison between the 2 groups was statistically significant (P<0.05). The SDS score of the experimental group was (37.46±4.68) points and SAS score of (34.89±5.11) points. The values of each index were lower than those in the control group, and there were significant differences between the groups (P<0.05). Anastomotic fistula, atelectasis, and anastomosis occurred in the experimental group. The rates of mouth stenosis were 2.22% (1/45), 2.22% (1/45), and 4.44% (2/45), which were lower than those in the control group, and the clinical comparison was significantly different (P<0.05). Conclusion: Applying high-quality whole-course nursing to the clinical care of patients with esophageal cancer can improve the patient’s negative psychology, reduce postoperative adverse reactions, and directly improve the patient's nursing satisfaction.