Objective: To explore the effect and clinical value of personalized nursing intervention according to Comprehensive Geriatric Assessment (CGA) on the quality of life in elderly patients with chronic diseases. Methods: A total of 300 elderly patients with chronic diseases were randomly divided into control group (n=150) and observation group (n=150). The patients in the control group were treated with routine nursing. On the basis of routine nursing, the observation group was treated with personalized nursing intervention based on CGA. Before intervention and at six months after discharged, two groups were assessed by using the quality of life scale, and their effect on quality of life and satisfaction rate of treatment and nursing work were compared before and after the intervention. Results: After the intervention, the scores in the elderly patients with the observation group in physiology, psychology, independence, social relations, environment, and general quality of life were higher than those of the control group (t=4.998, 4.937, 7.174, 5.106, 4.087, all P<0.05), and differences were statistically significant, and nursing satisfaction at six months after discharged were significantly higher than that of the control group (χ 2 =5.556, P<0.05). Conclusion: Personalized nursing intervention based on CGA can improve the nursing of elderly patients with chronic diseases and improve the satisfaction of patient during hospitalization and nursing after discharged, then improve the quality of life of patients.