Oral squamous cell carcinoma (oscc) is the fifth most common cancer worldwide and the number of cases is increasing regularly in the developing world. The effective detection of oscc at its early stages becomes necessary for proper treatment due to limited understanding of the critical pathways during oncogenesis. Signal transducer and activators of transcription (Stats) are an important group of transcription factors, which contribute to tumorigenesis due to their intimate connection to growth factor signalling, apoptosis, and angiogenesis. They also play a critical role in immune responses and hence defective Stat signalling could favour tumour development by compromising immune surveillance. The role of Stat5A in mammary gland carcinoma and leukaemia has already been reported. We for the first time report here the constitutive activation of Stat5A as one of the early events in tobacco mediated-oscc in the eastern Indian population, which can be used as a potent prognostic molecular marker.