Hemodialysis (HD) patients face a common problem of malnutrition due to poor appetite. This study aims to verify the appetite alteration model for malnutrition in HD patients through quantitative data and the International Classification of Functioning, Disability, and Health (ICF) framework. This study uses the Mixed Method-Grounded Theory (MM-GT) method to explore various factors and processes affecting malnutrition in HD patients, create a suitable treatment model, and validate it systematically by combining qualitative and quantitative data and procedures. The demographics and medical histories of 14 patients were collected. Based on the theory, the research design is based on expansion and confirmation sequence. The usefulness and cut-off points of the creatinine index (CI) guidelines for malnutrition in HD patients were linked to significant categories of GT and the domain of ICF. The retrospective CIs for 3 months revealed patients with 3 different levels of appetite status at nutrition assessment and 2 levels of uremic removal. In the same way, different levels of dry mouth, functional support, self-efficacy, and self-management were analyzed. Poor appetite, degree of dryness, and degree of taste change negatively affected CI, while self-management, uremic removal, functional support, and self-efficacy positively affected CI. This study identified and validated the essential components of appetite alteration in HD patients. These MM-GT methods can guide the selection of outcome measurements and facilitate the perspective of a holistic approach to self-management and intervention.