As water consumption increases due to industrialization and global population growth, climate change and urbanization exacerbate the limited available freshwater resources. To counter the challenge water desalination has been used to provide potable water that is ready for human consumption. However, most of the existing water desalination techniques have persistent drawbacks despite decades of development. Thus, a need for efficient and sustainable techniques is urgent. One of the emerging water desalination techniques is hydrate-based desalination. While clathrate has been a nuisance in the oil and gas industry, it has been investigated in several applications including water desalination. This work investigates thermodynamic effectiveness of two hydrate formers in the presence of chloride salts. Methane or carbon dioxide with Tetra n‑butyl ammonium bromide have been used as formers. While the presence of salts depresses the pressure effect on semiclathrate equilibrium on the tested range, it does not have a clear effect at low TBAB concentration. Thus, based on this study using a low concentration of TBAB (20 wt%) with low to moderate pressure of carbon dioxide would yield the most favorable thermodynamic conditions for hydrate-based desalination.