Updated project metadata. The practice of using chewing tobacco is common in certain socio-economic sections of southern Asia particularly in the Indian subcontinent. The molecular mechanism of smokeless tobacco which leads to malignancy is unclear. Chewing tobacco demonstrates a carcinogenic effect through chronic and not acute exposures. Using a cell line model, we studied the chronic effects of chewing tobacco on the proteome in normal oral keratinocytes (OKF6/TERT1). We carried out iTRAQ-based quantitative proteomic analysis of the untreated and chewing tobacco treated oral keratinocytes. LC-MS/MS analysis of this cell line pair resulted in the identification of 3,638 proteins of which 408 were found to be differentially expressed.