This study aims to explore the potential mediation role of person-centeredness between the effects of the work environment and nurse reported quality and patient safety. A quantitative cross-sectional survey collected data from 1055 nurses, working in medical and surgical units, in twelve Malaysian private hospitals. The data collection used structured questionnaires. The Hayes macro explored the mediation effect of person-centeredness between the associations of work environment dimensions and care outcomes, controlling nurses’ demographics and practice characteristics. A total of 652 nurses responded completely to the survey (61.8% response rate). About 47.7% of nurses worked 7-h shifts, and 37.0% were assigned more than 15 patients. Higher workload was associated with unfavorable outcomes. Nurses working in 12-h shifts reported a lower work environment rating (3.46 ± 0.41, p < 0.01) and person-centered care (3.55 ± 0.35, p < 0.01). Nurses assigned to more than 15 patients were less likely to report a favorable practice environment (3.53 ± 0.41, p < 0.05), perceived lower person-centered care (3.61 ± 0.36, p < 0.01), and rated lower patient safety (3.54 ± 0.62, p < 0.05). Person-centeredness mediates the effect of nurse work environment dimensions on quality and patient safety. Medical and surgical nurses, working in a healthy environment, had a high level of person-centeredness, which, in turn, positively affected the reported outcomes. The function of person-centeredness was to complement the effects of the nurse work environment on care outcomes. Improving the nurse work environment (task-oriented) with a high level of person-centeredness (patient-oriented) was a mechanism through which future initiatives could improve nursing care and prevent patient harm.