The potential use of Spirulina subsalsa in marine cultivation is important for biomass and phycocyanin production; however, little is known about its mechanism of salt adaptation. Here we present a draft genome sequence for the halotolerant cyanobacterium Spirulina subsalsa FACHB-351 (5.3 Mbp). The sequence is predominantly distributed in signal transduction, cell growth and adaptation, and carbohydrate metabolism, which possibly allows the strong salt adaptation of FACHB-351. No genes directly related to bacterial toxins suggests a low risk of FACHB-351 threatening human or animal health. A set of genes annotated in the GO database were not assigned in the KEGG database, and some genes of essential enzymes, like HO and DVR for phycocyanin and chlorophyll, were not found, which suggests a presence of possible yet-to-be-discovered pathways in FACHB-351. The availability of a genome sequence will facilitate investigations into S. subsalsa phycocyanin biosynthesis and permit optimal strategies to improve commercial phycocyanin production.