Febrile neutropenia (FN) is responsible for considerable morbidity and mortality in cancer patients. Aim of the study: the aim was to evaluate the effect of educational protocol for cancer patients with chemotherapy-associated FN on self-efficacy. Patients and Methods: Research design: Pre and post-test design was utilized. Setting: Oncology Department and Outpatient Oncology Clinics at Assiut University Hospital. Sample: A purposive sample of 120 male and female adult cancer patients with chemotherapy-associated FN. Tools: Tool I-Interview questionnaire sheet. Tool II: Patient activation measure. Results: Highly statistical significant differences were found between pre-test and post-test among the studied patients regarding the four stages of patient activation measure, total patient activation measure, and self-efficacy assessment,(P< 0.001). Conclusion: The educational protocol had a statistical significant positive effect on the self-efficacy of cancer patients with chemotherapy-associated FN. Recommendations: Simple educational booklets for cancer patients with chemotherapy-associated FN should be available in all Oncology Units and Outpatient Oncology Clinics. Further studies on larger sample from different geographical areas in Egypt to generalize the results and collect in depth knowledge about FN.