Background: Cancer affects millions of people in the world each year, leading many to face the difficult road of chemotherapy. When cancer patients are ill-prepared for chemotherapy treatments, they often tend to envision the worst-case scenarios, possibly making the anticipation more difficult than the event itself. In Ethiopia evidence on self-care behavior on chemotherapy and associated factors is limited. So this study is aimed to fill the gap. Objectives: To assess self-care behavior and associated factors among cancer patients who are on chemotherapy treatment at Tikur Anbessa Specialized Hospital Addis Ababa, Ethiopia 2018. Methods: Institution based cross-sectional study design was conducted on sample study of 254 study participants at Tikur Anbessa Specialized Hospital using simple random sampling techniques. Face to face interview with structured questionnaire was used to collect data. Prior to data collection 5% pretest was done to ensure the quality of data. Data was entered in to EpI –data version 4.2 and exported into SPSS versions 24 for analysis. Descriptive statistics used to describe the study participants with major independent and dependent variables' including frequencies, proportion, mean and standard deviation was demonstrated by using tables, graphs and texts. Bivariate and multivariate logistic regression was used to look for association between predictors and dependent variable. Crude and adjusted odds ratios with the corresponding 95% confidence intervals were computed. Result: In this study a total of 254 clients were participate patients of were from 34(13.4%) in patient and 220(86.6%) were from out patients. The study found that there was a poor selfcare behavior of chemotherapy patients and also age, income, educational level, occupation, cancer type, information from health care provider and fatigue had significantly associated with self-care of chemotherapy patients. Conclusions and recommendation Self-care behavior performed by studied patients was insufficient to provide complete relief of the side effect due to inadequate information about the side effects of chemotherapy and how to manage it. This needs intensive awareness creation campaigns on self-care behavior on chemotherapy patients to complement health education in health facilities.