Objective. To explore the application effect of medical care integration combined with family intervention under the evidence-based nursing mode on child patients with severe hand-foot-mouth disease (HFMD) and its influence on intestinal function. Methods. 120 child patients with severe HFMD admitted to Qilu Children’s Hospital of Shandong University from January 2019 to January 2020 were selected as the research object and randomly divided into group A and group B, with 60 cases each. Conventional nursing was performed on patients in group B, and medical care integration combined with family intervention under the evidence-based nursing mode was performed on patients in group A. Patients were assessed after the intervention using the hospital-made treatment adherence scale, PedsQLTM 4.0 (Pediatric Quality of Life Inventory Version 4.0) scale, and the faces pain scale-revised (FPS-R). The levels of gastrointestinal function indicators such as serum endotoxin (ET), diamine oxidase (DAO), and d-lactic acid (D-LA) were measured before and after the intervention, and recovery such as time to clear fever and time to relief of oral pain were recorded in both groups. Results. Children in group A had significantly higher compliance in diet, behaviour, exercise, and medication than group B ( P < 0.05 ); the time to clear fever, time to relief of oral pain, time to healing of oral ulcers, time to relief of skin herpes, time to hospitalization, and time to eating were shorter in group A than those in group B ( P < 0.001 ); all scores on the PedsQLTM 4.0 scale were higher in group A than those in group B after the intervention ( P < 0.001 ); ET, DAO, and D-LA levels decreased in both groups after the intervention, with group A having lower levels than group B ( P < 0.001 ), in addition, group A had lower eating pain scores after the intervention ( P < 0.05 ). Conclusion. Medical care integration combined with family intervention under the evidence-based nursing mode can effectively improve the treatment compliance of child patients with severe HFMD, accelerate their recovery progress, ensure a better prognostic quality of life and gastrointestinal tract function, and reduce the eating pain, indicating that such comprehensive nursing intervention mode should be promoted in practice.