Background: Nurses as the main human resource in coping with COVID-19 face many challenges and problems. Therefore, the present study aimed to explain the experiences, challenges, and adaptation strategies of nurses in taking care of patients with COVID-19 with a qualitative approach.Methods: The present study was conducted with a qualitative conventional content analysis approach among 30 nurses working in wards for COVID-19 patients, in Tehran hospitals. Access to participants and data collection was done through purposive sampling, snowball sampling and semi-structured interviews. Data were analyzed using qualitative content analysis (conventional) and MAXQDA-18 software. Guba and Lincoln criteria were observed to evaluate the quality of research results.Results: From data analysis, 2 main categories and 16 subcategories were obtained, including (1) experiences and challenges (lack of protective equipment, high work pressure, marginalized physical health, problems related to the use of protective equipment, getting excluded, lack of supportive work environment, problems related to patients, psychological problems, fear, marginalized personal and family life and the challenge of communication with patients' families) (2) Strategies for adapting to working conditions (performing religious-spiritual activities, creating an empathetic atmosphere in the workplace, spiritualizing their work , trying to convince the family and gain their support, strengthening sense of self-worth and responsibility).Conclusion: The working conditions for nurses can be improved through providing adequate protective equipment, providing a suitable work environment and more social and financial support, more attention to the physical and mental health of nurses and considering appropriate mechanisms for nurses to communicate with their families and patients' families.