Present study deals with the regulation of SA induced Ca2+-mediated NO signaling in cyanobacterium Anabaena PCC 7120. Nickel (Ni2+)-toxicity strongly inhibited growth (DW), exopolysaccharides, photosynthetic pigments, PSII photochemistry (OJIP transient parameters: Fm, Fv, Fm/Fo, Fv/Fo, Ψo, ФPo, ФEo, Area, N, and PIABS were suppressed; while Fo, Fo/Fm, Fo/Fv, Sm, ФDo, ABS/RC, TRo/RC, ETo/RC and DIo/RC were raised), nitrogen metabolism status and non-enzymatic antioxidant system by increasing intracellular Ni2+ accumulation and excessive ROS production. However, salicylic acid (SA), calcium (CaCl2) and sodium nitroprusside (SNP) addition to the culture medium counteracted on negative impact of Ni2+ thereby improving the growth. Further, to investigate the relation between Ca2+ and NO, when c-PTIO was supplemented to Ni+SA+Ca and EGTA to Ni+SA+NO treated culture medium, the recovery on above studied traits caused due to Ca2+ and NO was arrested even in presence of SA to Ni2+-stressed Anabaena cells thereby suggesting the signaling behavior of Ca2+ and NO in SA induced pathway; however, the impact was worsened under c-PTIO supplemented Ni+SA+Ca than EGTA supplemented Ni+SA+NO treatment thereby suggesting key role of NO in SA-induced Ca2+-mediated signaling. Additionally, NO accumulation, intracellular Ni2+ accumulation, ROS and indices, and non-enzymatic antioxidant system were also examined that showed varied results.