Background: Cancer pain management at home is a complicated and multidimensional experience that affects the foundational aspects of patients and their families' lives. Understanding the pain relief process and the outcomes of palliative care at home is essential for designing programs to improve the quality of life of patients and their families. Objective: To explore family caregivers and patients' experiences of pain management at home and develop a substantive theory. Design: The study was carried out using a grounded theory methodology. Setting/Participants: Twenty patients and 32 family caregivers were recruited from Oncology wards and palliative medicine clinics in the hospitals affiliated to Iran University of Medical Sciences using Purposeful and theoretical sampling. Results: The core category in this study was "pain relief with the least harm." Other categories were formed around the core category including "pain assessment, determining the severity of pain, using hierarchical approaches to pain relief, assessing the results of applied approaches, determining the range of effectiveness, and barriers and facilitators of pain relief." The substantive theory emerged from these categories was "Pain management process in cancer patients at home: Causing the least harm" that explains the stages of applying hierarchical approaches to pain relief, family care givers try to make decisions in a way that maximize pain relief and minimize damage to the patient. Along with using a hierarchical pattern, the process is featured with a circular pattern at broader perspective, which reflects dynamism of the process. Conclusion: The inferred categories and theory can expand knowledge and awareness about the stages of pain relief process, the pattern of using pain relief approaches, and the barriers and facilitators of pain relief process at home. Health-care professionals may use these findings to assess the knowledge, skill, capability, problems, and needs of family caregivers and patients and develop supportive and educational programs to improve the efficiency of pain relief process at home and improve the patients' quality of life.