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Introduction Compassion is a core value in person-centred nursing and is essential in the care of patients with cancer. However, existing measurement instruments often fail to capture the cultural, ethical and relational dimensions of compassion as perceived by patients within specific sociocultural contexts. This study aims to develop and psychometrically evaluate the compassion perception in nursing care (CPNC) instrument for patients with cancer, reflecting the local sociocultural context of cancer care in Iran.Methods and analysis A sequential exploratory mixed-methods design (qualitative→quantitative) will be employed. For instrument development, the study will proceed through three sequential stages. Stage 1 will involve qualitative concept elicitation and development of a patient-derived conceptual model and operational definition of perceived compassion. Stage 2 will involve questionnaire development and mixed-methods content validity assessment. Stage 3 will comprise quantitative psychometric evaluation of the refined CPNC instrument. Content validity will be assessed through cognitive interviews, patient-based quantitative assessment and expert-based evaluation. Psychometric testing will include exploratory and confirmatory factor analyses, internal consistency, test-retest reliability, measurement error and interpretability assessment.Ethics and dissemination Ethics approval was obtained from the Research Ethics Committee of Tarbiat Modares University (IR.MODARES.REC.1404.033), and the study will be conducted in accordance with the principles of the Declaration of Helsinki. The findings will be disseminated through peer-reviewed publications and presentations at national and international oncology nursing conferences.