Oral submucous fibrosis (OSF) is a chronic complex potentially pre-malignant condition caused by chewing areca nut and other irritants. It is an insidious process characterized by Juxta-epithelial deposition of fibrous tissue in the oral cavity and pharynx. OSF is very common in Southeast Asia and also now a days increase in Europe and North America. The aim of this study to compare the effectiveness of intralesional injection of triamcinolone and hyalurunidase versus intralesional injection of triamcinolone plus injection hyalurunidase with oral colchicine. The study included 60 patients of clinically diagnosed case of oral submucous fibrosis. Patients were divided into two Groups A and B. Group A patients received combination intralesionsl injection of triamcinolone acetonide 10mg/ml in 1ml with injection hyalurunidase 1500IU in 2ml with injection 2% lidocaine 7ml. 15 days interval in 3 months and Group B received intralesional injection of triamcinolone acetonide 10mg/ml in 1ml with injection hyalurunidase 1500IU in 2ml with injection 2% lidocaine 7ml in each 15 days interval for 3 months with oral colchicine 0.5mg twice daily for 3 months. Diagnosis based on burning sensation of mouth, blanching of mucosa, ulceration in oral cavity and also reduced mouth opening. Follow up assessment was done at intervals 1st follow up on 21st days after starting of treatment then 2nd follow up after 3 months and last 3rd follow up after 6 months. Before starting of treatment all patients were properly explained about the study and took their written consent. Much more improvement occurred in Group B patients, reducing in burning sensation and also increases in opening of mouth. In both groups blanching mucosae were improved. Treatment regimen of Group B is more effective in increasing mouth opening and improves burning sensation of oral cavity. No side effects were seen in both groups' patients.