BACKGROUND: Oral Submucous Fibrosis is a potentially premalignant disorder well known for its chronic and resistant nature. Currently available treatment with local injection of corticosteroids with Hyaluronidase is effective to some extent. The aim of the study was to evaluate whether the efficacy of the current treatment modality for submucous fibrosis can be improved by adding either oral lycopene or oral anti-oxidants along with local injection of steroids. METHODS: This study was conducted from July 2012 to August 2014 A total of 38 patients were included under this study with either grade 3 or 4 submucous fibrosis they were randomly divided in to 2 groups consisting 19 patients each Group 1 were given oral lycopene of dose 16mg/day along with once weekly intralesional injection of steroids and Hyaluronidase. Group 2 were given only once weekly intralesional injection of steroids and Hyaluronidase. Mouth opening recorded from baseline to 6 weeks. Cases were followed up for 6 months thereafter. RESULTS: There was significant increase in mouth opening in both the groups. The results were statistically significant between Group 1 and Group 2. Group 1 patients responded better than the other group and P value < 0.001. CONCLUSION: Lycopene in combination with intralesional steroids and Hyaluronidase, is highly efficacious in improving the mouth opening and reducing other symptoms in patients with Oral Submucous Fibrosis.