Background: Cancer patients experience negative changes in their quality of life, and some of them can have physical side effects and mental health problems. Lifestyle changes related to exercise and nutrition can improve the health of these cancer patients. Aim: the aim of this study was to develop life style guideline for patients undergoing chemotherapy in Port Said City. Subjects and Method: Design: A quasi-experimental (one-group pretest-posttest) design.Setting: The present study was at health insurance hospital namely El-Tadamon hospital which have chemotherapy center in Port Said City. Sample: The purposive sample of the study included 66 cancer patients undergoing chemotherapy in the pre mentioned hospital. Tool: One tool used to gather the required data, namely, Health-Promoting Lifestyle Profile II (HPLPII). Results: The study revealed that 69.7% of the patients were females and 40.9% of them age range from forty to fifty years old. The majority of patients 74.2% had pain as a said effect of chemotherapy. In addition, in posttest, interpersonal relations gained the highest mean score (29.23±3.64), followed by responsibility for health (26.38±2.94). Conclusion: It can be concluded, a highly statistically improvements after implementation of guideline in all domains and overall scores of lifestyle from pre to post guideline implementation, furthermore, in post guideline implementation, a statistically significant associations between age and domains of physical activity, nutrition, interpersonal relations, overall of lifestyle a statistical associations between level of education and domains of physical activity, spiritual growth, stress management were detected, Recommendations: Designing and applying regular health education program for patients undergoing chemotherapy to improve maximum quality of life.