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Aim: To assess various cytological changes for predicting radiosensitivity of oral squamous cell carcinoma by exfoliative cytology.Materials and methods: Histologically proven 30 cases of oral squamous cell carcinoma who underwent fractionated radiotherapy in a dose of 45-60 Gy in 5 fractions/week were enrolled in the study. The exfoliative cytology smear was evaluated on lesional and adjacent oral mucosa before radiotherapy, during radiotherapy (8 and 11th fraction) and post radiotherapy (4, 6 and 8 weeks). Various parameters like multinucleation, cellular enlargement, nuclear enlargement, cytoplasmic vacuolation, cytoplasmic granulation, leukocytic infiltration were evaluated.Results: Statistical significant values were seen in the intergroup comparison of all the parameters when compared adjacent mucosa and normal mucosa for leukocytic infiltration in pretreatment smear. Conclusion:The study showed that radiation-induced cytological changes in oral squamous cell carcinoma have a significant dose-related increase. This dose-response relationship and the high intratumoral variations suggest that serial assay of these changes has potential use for radiosensitivity prediction.Clinical significance: Radiosensitivity prediction can be evaluated by means of cytological smears in one stop crisis centre (OSCC) individuals subjected to fractionated radiotherapy by evaluating the cytological parameters.