The aim of this study is to assess the genotoxic effect of occupational exposure to antineoplastic drugs on oncology nurses in order to propose a strategy for adequate safety. The study included 20 oncology nurses from the Farhat Hached university hospital-Sousse (Tunisia) exposed to antineoplastic drugs compared to 20 controls. The two groups were paired according to sex, age, and smoking habits. The genotoxic risk assessment was carried out by the micronucleus test and chromosomal abnormalities. The search for the clinical effects of cytostatic drugs was based on a questionnaire. Determination of the level of the exposure to cytostatic was performed by calculation of the index of the exposure to these drugs. The median age of nurses was 36 years. A female prevalence (80%) was noted. The exposed period to cytostatic was 6.1 years. The middle index of cytostatic contact calculated for the whole of the nurses, was of 1.5. However this index becomes higher (>3) in nurses working at day care. A significant increase in frequencies rates for both micronucleus (9.40‰ vs 4.35‰) and chromosome abnormalities (1.85% vs 0.30%) were noted in exposed group more than controls. In conclusion, application of genotoxic tests may be useful to detect cytogenetic damage related to occupational exposure to a potentially cancerogenic environment. Results of the present biomonitoring study emphasize the need for developing safety programs.