Objectives: The objective of this study was to describe self-care practice during radiotherapy for cancer and to identify potential differences between practitioners and non-practitioners of self-care regarding sociodemographic, clinical, functional, and quality-of-life-related characteristics. Methods: In this descriptive study, 439 patients (87% response rate) undergoing radiotherapy responded to a study questionnaire regarding self-care, sociodemographic, clinical (eg, experienced symptoms), functional, and quality-of-life-related characteristics. Results: Of the 439 patients, 189 (43%) practiced at least one self-care strategy, while 250 (57%) did not. In total, the patients described 332 self-care practices, resulting in 14 different categories of self-care strategies. The 5 most common indicators of practicing self-care were fatigue, general wellbeing, psychological symptoms, nausea, vomiting and improving physical condition. The 5 most common self-care strategies were physical activity, increased recovery, healthy eating, distraction, and skincare. Patients who were married, were older than 69, patients with less education than university education, patients undergoing a combination of internal and external radiotherapy, patients experiencing fewer than 8 symptoms, and better quality of life, practiced self-care to a lower extent than did other patients. Functional capacity did not differ between self-care practitioners and non-practitioners. Conclusion and Implications for Practice: Of the patients undergoing radiotherapy, slightly less than half practiced self-care during an ordinary week of radiotherapy. Because older and less-educated patients were less likely to practice self-care, cancer care practitioners should consider paying particular attention to helping such patients with their self-care practice.