Chemoresistance is one of the major factor in treatment failure of OSCC. Chemotherapy successfully eliminates the rapidly dividing cells in tumor mass but poorly targets the slowly dividing cells. Due to acquired chemoresistance, the patients experience continued tumor growth with metastatic disease. However, the exact causative factors responsible for it are yet to be explored. The chemoresistance phenotypes can be attributed to reduced apoptosis, enhanced cancer stem cell population, altered metabolic activity and decreased drug accumulation. All these hallmarks are endpoint events when the tumor cells have already acquired drug resistance. Till date, majority of the study engaged in analyzing either the parental drug sensitive cells or late drug resistant cells to understand the molecular mechanism for chemoresistance. However, the intermediate or transition phase of tumor cells (early chemoresistance) during the process of acquired chemoresistance is poorly characterized.