Introduction: There is a growing concern regarding self-care and chemotherapy side effects. The present study aimed to assess the effectiveness of self-care measures on knowledge, self-efficacy, and performance status among cancer patients undergoing chemotherapy. Methods: A quasi-experimental study was conducted in Dr. Kamatchi Memorial Hospital, India. Using purposive sampling technique, 200 cancer patients were selected. Patients were interviewed using semi-structured knowledge questionnaires, Modified Stanford Patient Education Research Center Self-efficacy scale, deliberate self-efficacy with rating scale under four subheadings, and ECOG Performance Status Scale with 5– point grading scale i. e., dead to fully active. Results: There was adequate knowledge (95%) on self-care measures after the intervention. The mean score was significant, i. e., 21. 33 (2. 25), which had difference between post-knowledge score in experimental and control was statistically significant at P < 0. 001 level. The majority of patients reported a high self-efficacy level (t = 198. 60, P < 0. 001). In addition, despite self-efficacy and knowledge the performance status observed at each cycle, i. e., 4 cycles had mean score of t = 32. 13, P < 0. 001, showed high level of performance status. Conclusion: The study revealed that the self-care measures during each cycle had improved the selfefficacy and performance status to high level, which in turn reduced the side effects of chemotherapy to the certain level.