Introduction/Objective: Lycopene is effective in managing OSMF. Effect of Lycopene on reducing the Micronuclei frequency __ampersandsignamp; correlation of Serum lycopene and BMCF has not been studied in OSMF. This study is designed to assess the effect of lycopene in reducing, clinical symptoms, as assessed by mouth opening (MO), Tongue protrusion (TP), Cheek flexibility (CF), Palpable fibrotic bands (FB), burning sensation (BS), and the genotoxicity in oral submucous fibrosis patients as assessed by buccal micro-nucleated cell frequency (BMCF). Methods: A randomized, placebo-controlled, triple blinded trial, of 3 months duration. Out of 40 OSMF patients reported during the study period, 36 OSMF patients aged between 17-70 years who fulfilled the inclusion criteria were randomly divided into two groups equally- Group 1 received lycopene 16 mg (Lycored __ampersandsignreg; 4mg 2 BID) per day, and Group 2 received placebo capsules (similar quantity). The outcomes MO, TP, CF, FB, BS, serum lycopene levels and BMCF were recorded at the baseline and the end of 3 months. Results: In Group 1 compared to Group 2 clinical signs and symptoms MO, TP, BS improved significantly. Serum lycopene levels improved and BMCF reduced significantly. BMCF showed a negative correlation with the serum lycopene levels. Conclusion: The results of the present randomized controlled study throw more light on the role of lycopene in combination with habit cessation in OSMF, both in the improvement of most of the clinical symptoms and as a potent antigenotoxic agent, by reducing BMCF.