After emerging as a first-team regular at the La Liga outfit this season, the 21-year-old is said to have caught the attention of Manchester United.
However, according to L'Equipe, Southampton are one of the frontrunners for Salisu, who would cost in the region of £10.8m.
While the Saints are willing to bring the centre-back to the Premier League, it is claimed that they are yet to agree terms with Ghanaian.
Although Rennes have also been suggested as a potential destination, Salisu is said to prefer a switch to England.
The player still has two years remaining on his Valladolid contract.