To examine the association between mutuality and quality of life in nurse-patient dyads. A cross-sectional multi-centre study was conducted. The study was conducted in five tertiary hospitals in Italy. We enrol both inpatients and outpatients with chronic diseases and their nurses with a convenience sampling. One-hundred ninety-two dyads participated to the study. A self-assessment instrument including the Short-Form 12 Health Survey (SF-12), and the Nurse Patient Mutuality in Chronic Illness scale (NPM-CI scale), in the two versions-one for patients and one for nurses, was administered. The effects of nurse-patient mutuality on the physical and mental quality of life of nurses and patients were estimated with a series of actor-partner-interdependence models (APIM). Patients' and nurses' perceptions of their mutuality were positively correlated. For patient mental quality of life, there was a statistically significant actor effect both for patients, and for nurses. There was also a consistent statistically significant partner effect for patient mental quality of life. There were no statistically significant actor or partner effects for the nurses' and patients' physical quality of life. This construct may be influenced by additional components, further studies are needed. Mutuality between nurses and patients in chronic diseases influence both patient and nurse quality of life. Our results support the importance of taking a dyadic perspective when considering mutuality and quality of life in nurse-patient dyads. Nurse-patient mutuality is an indicator of a high-quality relationship, which allows shared goals and shared decision-making. Quality of life is one of the most important outcomes for chronic conditions patients and is an indicator of well-being. Quality of life is also an important variable in healthcare professionals' lives. Little is known about the association between mutuality and quality of life in nurse-patient dyads. Mutuality has an actor effect on patient's and nurse's quality of life and has a negative partner effect on patient's quality of life. The understanding of mutuality and interdependence within the dyad, could increase mental quality of life in nurse-patient dyads. STROBE checklist for cross-sectional studies was followed in this study. Patients were involved in the sample of the study.