Response of two native cyanobacterial strains to uranium exposure was studied. Anabaena L-31 exhibited higher tolerance to uranium as compared to Anabaena 7120. Uranium exposure differentially affected the proteome profiles of the two strains. Anabaena L-31 showed better sustenance of photosynthesis and carbon metabolism. Anabaena L-31 displayed superior oxidative stress defense than Anabaena 7120.