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Aims/Background Acute myeloid leukemia (AML) is a hematologic malignancy that often requires prolonged hospitalization and intensive treatment, leading to substantial psychological distress and impaired quality of life (QoL). The positive psychology-based PERMA (positive emotion, engagement, relationships, meaning, and accomplishment) model encompasses five dimensions and has demonstrated benefits in various chronic diseases, though evidence in AML remains limited. This study aims to investigate the effects of PERMA model-based nursing on psychological well-being and QoL in hospitalized AML patients. Methods We conducted a single-center, retrospective case-control study of 555 AML inpatients admitted between March 2022 and March 2025. Patients received either PERMA model-based nursing (PERMA group) or conventional nursing (control group). Propensity score matching (PSM; 1:1; caliper = 0.2) was applied to balance baseline characteristics, resulting in 242 matched patients (121 per group). Psychological status was assessed using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), and QoL was evaluated using the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ‑C30). Results After matching, baseline characteristics were comparable across the two groups. In the control group, SAS scores increased significantly (p = 0.001) while SDS scores showed a slight decrease. Scores of global health status-quality of life (GHS-QoL), physical functioning (PF), emotional functioning (EF), and social functioning (SF) declined markedly (all p < 0.001); nausea/vomiting (NV) and appetite loss (AP) increased, diarrhea (DI) decreased, and financial difficulties (FI) increased significantly. In the PERMA group, SAS and SDS scores decreased significantly (both p < 0.001), PF declined (p < 0.001), role functioning (RF) improved (p = 0.024), while fatigue (FA), NV, AP, and FI all increased significantly. At discharge, the PERMA group recorded significantly lower SAS and SDS scores and higher GHS-QoL, EF, and SF scores than the control group (p < 0.01). Conclusion PERMA model-based nursing significantly alleviated anxiety and depression and improved key QoL domains in hospitalized AML patients. This structured, low-cost intervention is feasible in clinical practice and merits further validation in multicenter prospective studies.