Cancer is one of the leading causes of morbidity and mortality globally. A significant proportion of all patients with cancer require radiotherapy as part of their treatment. Cancer can be very terrifying for patients undergoing radiotherapy, especially when it undermines their ability to hope or cope. In Ghana, where religious and spiritual beliefs play a significant role in many individuals’ lives, understanding how these factors affect patients’ well-being during cancer treatment is crucial. This study examined the contribution of spirituality and religiousness to the quality of life (QoL) of cancer patients undergoing radiotherapy in Accra, Ghana. Pre-validated questionnaires were used to collect data that were analysed using the Statistical Package for the Social Sciences software (version 20). Patient interviews were also conducted and analysed thematically. Most of the respondents were female (n = 58, 65%), whereas 32 (35%) were male. The mean age of the respondents was 45.8 years (SD 12.9). All the participants of the study were religious and considered themselves to be either Christian (n = 82, 91.1%) or Muslim (n = 8, 8.9%). Approximately 93% of the participants relied on their spiritual beliefs to cope with cancer. Many patients reported that spirituality and religious coping are important aspects of their experience, potentially influencing their perceived QoL during radiotherapy. Most patients considered attention to spiritual concerns an important part of cancer care by doctors (88%) and nurses (85%). Five themes were identified from the analysis of the qualitative data. These themes indicated nuanced insights into how spirituality and religiousness influence the experiences of cancer patients. The findings of this study demonstrate the need to cater not only to bodily but also to emotional, social and spiritual needs that arise in the lives of cancer patients.