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Chromium existing in the biosphere in prominent two forms Cr (III) and Cr (VI) is a well-studied heavy metal. Cr (III) is considered as non-harmful and necessary element in diet whereas Cr(VI) is extremely toxic exerting various negative health impacts on human and other organisms. Mining activity is must for extracting economic minerals and a large number of people are related to these sites as worker or habitants and a major source of chromium exposure. Present chapter discusses genotoxic nature of chromium considering respiratory disease resulted from chromium exposure. The genotoxicity is illustrated in terms of chromium induced differential expressed genes (DEGs), transcription factors and microRNA regulating the DEGs and their gene ontology.