Betis’ latest defeat at the San Mames stadium left them with just one win in their last 10 La Liga games.
Great expectations were expected of the Andalusian side at the start of the season after they splashed the cash on the likes of Borja Iglesias and Nabil Fekir.
Betis are now 14th on the La Liga table, eight points above the relegation zone with 10 games remaining.
"Real Betis Balompie administration board have decided today that Alexis Trujillo will be in charge of the first team," a statement read.
"The former green and white player and captain, currently co-ordinator of the sporting area of the club, will be at the helm until the end of the current season.
"Humberto Alexis Trujillo Oramas was a Real Betis player for seven seasons, in which he played 264 official games in total. He has also been the head coach of the green and white for two games in the 2016/2017 season
"Also, the club would like to thank Joan Francesc Ferrer Sicilia 'Rubi' and his technical staff for all their services and wish them all the best in the future."
Betis will be looking for their first win after the coronavirus-enforced break when they take on Espanyol at home on Thursday.