In an attempt to reduce side effects of cancer chemotherapeutic drugs with the use of the natural product such as clove oil, as it considered that natural resources had always been a better supplement than chemicals in drug manufacture and disease treatment especially that chemicals often have hazardous short or long term side effects. The present study was carried out to compare the effect of combination of clove oil with 5-fluorouracil versus clove oil with cisplatin in management of head and neck squamous cell carcinoma cell lines. Material and methods: All tested sets were examined to evaluate cytotoxic effect of tested drugs by MTT assay, cell cycle analysis and level of apoptosis by flowcytometery. Conclusion: The cell cycle analysis demonstrated that the combination of cisplatin and clove oil exhibited an increase in the percentage of cell growth arrest during the G2/M phase compared to other tested and it exhibited an increase in the percentage of apoptotic cells during the Pre-G1 phase compared to other tested sets.