In India, nearly 1,392,179 cancer cases by the year 2020, and the most common 5 leading sites are breast, lung, mouth, cervix, and tongue. Trends in cancer incidence rates showed an increase in cancer in both sexes. Small and repeated exposure to chemotherapeutic agents was also dangerous because chemotherapeutic drugs are carcinogenic, mutagenic, and/or teratogenic. They can cause toxicity to multiple organs depending on the type of chemotherapeutic drug or site of exposure and can also be inhaled in a vaporous form. So, this research mainly focuses on preventing unintentional exposure and causing cancer from the exposure due to less knowledge and practice level. To assess the effectiveness of planned teaching program on knowledge and practice regarding safe handling of chemotherapeutic drugs among staff nurses in the hospital and to determine the relation between pre-test and post-test knowledge and practice score. Pre-experimental one-group pre-test and post-test designs were used. Data was collected with the help of a developed questionnaire and checklist from 30 staff nurses who were selected by the non-probability purposive sampling technique. The study was conducted at Rajiv Gandhi Cancer Institute and Research center, New Delhi. Data were collected before and after the planned teaching program. Post-test was taken after 4 days of planned teaching. The finding of the study revealed that the pretest means ± SD of knowledge was 15.64 ± 4.5 and in comparison to the mean ± SD post-test score was 20 ± 4.1 and the practice mean ± SD was 14.86 ± 1.06 and post mean ± SD test was 18.08 ± 0.94. And this shows that the ‘t’ table value was less than the ‘t’ calculated value which shows there was a positive relationship between the knowledge and practice and there is also a correlation between knowledge and practice. It also concludes that the planned teaching program was effective in the knowledge and practice of the staff nurses