Guzman, fired one day after Guadalajara dismissed Efrain Flores, became the sixth Mexican first division coach to lose his job since the 2008/09 season re-started in mid-January.
His dismissal appeared particularly ruthless as Santos Laguna are in the semi-finals of the CONCACAF Champions League with a 2-1 lead over fellow Mexicans Atlante following last week's first leg at home.
"It's the end of a cycle full of commitment and growth in which he gave great satisfaction to the fans and the institution," said the Torreon-based club in a statement.
The 43-year-old former Mexico international forward took over at the start of the 2006/07 season with Santos Laguna struggling in the relegation standings which are decided over three years.
Santos saved themselves from the drop by beating Cruz Azul 2-0 on the last day of the season and one year later won the 2007/08 Clausura championship.
Atlas, America, Tigres UANL and Morelia are the other clubs to have parted company with their coaches since January.
