The main aim of this study is to determine the various types of oral bacteria and yeast. Present in oral flora of head and neck cancer patients at different stages of chemo-radiotherapy, and compare it with the control group (patients with contralateral healthy mucosa). Seventy seven patients with proven history of squamous cell carcinoma were included in the study. The oral mucosa profile was assessed for bacterial manifestations in swab samples from both the sites of the patients. The grade of mucositis was charted out for all patients during the second and third week of radiotherapy. The study revealed that all isolated oral flora showed a non-significant increase during radiotherapy, while there was a decrease in oral flora in post RT. However, E. faecalis showed a non- significant decrease during RT, while Citrobacter showed an increase. Candida albicans showed 83% non- significant decrease post- radiotherapy. When these floras were correlated with grade of mucositis, an insignificant increase in flora was found in G2 and G3 stage of mucositis. In this study, the effect of radiation was evaluated on oral flora of head and neck cancer patients and compared with contralateral healthy mucosa of the patients. Various changes were observed during and after radiation therapy. In patients with head and neck cancer the normal oral flora are replaced by pathogenic flora during radiotherapy, and the latter is responsible for infections in post- radiation phase.