Aims and Objectives To investigate the association between perceived nurse–patient interaction and quality‐of‐life among nursing home residents, adjusted for loneliness, anxiety and depression. Background Symptoms of anxiety and depression are known to residents of nursing homes along with cognitive impairment, physical inactivity and low quality‐of‐life. Anxiety, depression and loneliness are found detrimental to NH residents' quality‐of‐life. The nurse–patient relationship is important for patient's well‐being, both in terms of illness and symptom management. Design Cross‐sectional design. Methods Data were collected in 2017 and 2018 from 188 residents in 27 nursing homes resided in two large urban municipalities in Middle and Western Norway. The inclusion criteria were: (1) local authority's decision of long‐term NH care; (2) residential stay 3 months or longer; (3) informed consent competency recognised by responsible doctor and nurse; (4) capable of being interviewed, and (5) aged 65 years or older. This article is executed in accordance with STROBE statement. Results Adjusting for age, sex, anxiety, depression and loneliness, perceived nurse–patient interaction was statistically significant to quality‐of‐life. While anxiety and depression showed insignificant estimates, loneliness demonstrated a significant relation with quality‐of‐life. Nurse–patient interaction and loneliness explained together 25% of the variation in quality‐of‐life. Conclusion This study suggests that loneliness is frequent as well as more detrimental to quality‐of‐life among nursing home residents compared to anxiety and depression. Furthermore, the present results show that the nurse–patient interaction represents an essential health‐promoting resource for Quality‐of‐life in this population. Relevance to clinical practice Staff nurses need to exercise their awareness of loneliness to meet residents' needs. Nursing educations should provide knowledge about nurse–patient interaction, and students as well as staff nurses in NHs should be trained, for instance by simulation, to use the nurse–patient interaction as a health‐promoting resource. Finally, loneliness represents a bigger challenge than depression and anxiety; accordingly, building nurses that are capable of meeting patients' needs and facilitate care that counteracts loneliness is highly warranted