Michael Laudrup's side welcome rock-bottom Sunderland to the Liberty Stadium on Saturday having not picked up three points in a home game in eight attempts since March.
Finishes of 11th and ninth over the last two seasons have been largely based on solid home form, and De Guzman is determined to help his side get back on track after two straight defeats before the international break.
"It will be difficult as we have lost our last two Premier League games," he said. "But it is a game we should win, we are at home and three points is mandatory.
"We have been playing well, we have just lacked goals at the crucial moment, it was like that at Southampton, we created a lot of chances but didn't score, hopefully our fans can help us change that on Saturday.
"We have had a number of difficult sides to play at home, but we had good results here last season and we can do so again.
"We haven't won here for a while but beating Sunderland would set a different tone for the games ahead."
Gus Poyet will be taking charge of the Black Cats for the first time since he replaced Paulo Di Canio, and De Guzman expects the Uruguayan to make an instant impact on the team.
"He is very different to their previous manager so there may be a different philosophy but we have to keep playing our football and the points will come from there," added the on-loan Villarreal midfielder.
"It's never easy for players or the coach coming in but it is a fresh new start for them and they will be looking forward to it and hope it is a positive move.
"But this is one of the most important weeks of our season. It will be great start if we win this week and fine motivation for our next two games against Kuban Krasnodar and West Ham.
"We have trained well and have some injured players back."
De Guzman sat out Holland's final two World Cup qualifiers due to a groin injury, but he is expected to be passed fit to start against Sunderland this weekend.