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Objectives Understanding maternal perceptions of the quality and safety of care serves as a crucial management tool for the planning and enhancement of health interventions. In Iran, where cultural norms emphasise mothers’ central role in caregiving and healthcare resources are often limited, incorporating their perspectives into nursing care strategies is essential. This study aimed to assess the perception of key nursing safety practices among Iranian mothers of children with leukaemia undergoing their first chemotherapy course.Design A longitudinal study.Setting Oncology wards of hospitals affiliated with Tabriz University of Medical Sciences.Participants Mothers of children with leukaemia.Results The mean perception score increased from 2.75 (out of 4) at baseline to 2.99 by week 4. The largest increases in perception were observed in patient identification and hand hygiene, with mean differences of 0.41 and 0.38, respectively. A significant increase in overall perception and subscales was observed (p<0.001). Mothers’ education level, economic status, child’s age, family size and the child’s leukaemia type (acute lymphocytic leukaemia vs acute myeloid leukaemia) were significantly associated with their perceptions.Conclusions Actively involving mothers in the care process enhances their perceptions of safety and quality during hospitalisation. Supportive and educational interventions are needed to further improve the safety and quality of nursing care.