Objective. To explore the effect of the comfortable intervention-based nursing mode under the quality nursing intervention combined with Internet mobile health on the quality of life (QOL) and psychological status of patients with acute cerebral infarction (ACI). Methods. 90 ACI patients treated in our hospital (June 2019-June 2020) were chosen and equally split into the experimental group (EG) and control group (CG) according to the order of admission. CG received routine nursing, while EG received the comfortable intervention-based nursing mode under the quality nursing intervention combined with Internet mobile health to compare the clinical indexes between the two groups. Results. Compared with CG, EG after intervention achieved obviously higher SS-QOL, ESCA, and GCQ scores ( P < 0.001 ), and lower MSSNS and NIHSS scores ( P < 0.001 ). Conclusion. The application of the comfortable intervention-based nursing mode under the quality nursing intervention combined with Internet mobile health effectively improves QOL and alleviates the negative emotions of patients. Compared with routine nursing, this model has higher application value, and further research of the joint intervention will help build better a solution for patients.