This study aimed to investigate the efficacy of PERMA-based nursing intervention in reducing the fear of disease progression in parents of children with acute leukemia. A quasi-experimental design was employed, enrolling children with acute leukemia and their parents at the First Hospital of Jilin University, who were divided into intervention and control groups. The intervention group received an 8-week positive nursing intervention covering eight themes, including positive self-awareness, emotion regulation, and cultivation of positive qualities. The control group received standard nursing care. Results indicated that after the intervention, the total fear of parental disease progression scores in the intervention group were significantly lower than those in the control group, and the positive psychological capital scores were significantly higher. Additionally, the scores for positive coping strategies also significantly increased. This study confirmed the effectiveness of PERMA-based positive psychological intervention in enhancing the psychological capital and happiness of parents of children with acute leukemia, providing a new perspective for clinical psychological nursing.