Background and objectives: Cancer is a group of disease which comprises of more than 200 diseases. They are considered as a disease of the aged; although the majority of cases that is about (77%) cases are diagnosed to have cancer at the age of 55 years. The study aimed to assess the effectiveness of educational program on knowledge regarding safe handling of cancer drugs among staff nurses. Materials and methods: A quantitative research approach is adopted with the pre-experimental (one group pre-test post-test only) research design and convenient sampling technique was used to select the sample and structured questionnaire was used to collect the data among 60 staff nurses working in Mahatma Gandhi Medical College Research Institute, Puducherry. The pre-test was conducted by using structured questionnaire and the educational program (power point) was implemented to staff nurses regarding safe handling of cancer drugs. The post-test was conducted after 7 days of pre-test. Results: The results shown that the effectiveness of educational program on knowledge regarding safe handling of cancer drugs between the pre-test and post-test, the p value was highly significant at p < 0.001 level. Conclusion: It was implied that educational program regarding safe handling of cancer drugs was effective.