The 23-year-old spent the first half of the season at Eskisehirspor in Turkey, but is now heading for Seville.
A club spokesman said: "Alfred N'Diaye has joined Real Betis on loan for the rest of the season."
N'Diaye, who joined the club from Bursaspor in January last year, has made 16 senior appearances for the Black Cats.
Meanwhile, defender Modibo Diakite is close to sealing a loan move to Italian club Fiorentina.
Press Association Sport understands the 26-year-old Frenchman was heading for Italy on Thursday after failing to make his mark at the Stadium of Light.
Diakite was one of 14 new signings to arrive at the Stadium of Light from Lazio during the summer, but he has managed only eight senior appearances for the club to date.
He has slipped in the pecking order this month with the arrival of Argentinian defender Santiago Vergini on loan from Atletico Fenix.