Villarreal, who pipped Sevilla to fourth place last season and a Champions League berth, begin the second round of La Liga action in the bottom two of the standings after suffering a 5-0 loss at the Nou Camp before the international break.
In contrast, Sevilla are in fifth spot after starting their campaign with 2-1 derby win over big-spending Malaga in what was coach Marcelino Garcia Toral's league debut in charge at the Ramon Sanchez Pizjuan stadium.
Sevilla's win was largely down to a brilliant performance from Negredo, who scored both his side's goals and was a constant menace to the Malaga defence.
Negredo also netted Spain's first two goals in Tuesday's 6-0 Euro 2012 qualifying win over Liechtenstein and Lopez - who was at Real Madrid at the same time as Negredo - knows his side need to keep a special eye on the 26-year-old.
"Negredo has progressed a lot, he's a player who has grown with time and he is at a great level. He is a very dangerous player and Sevilla will be a very difficult opponent because they have a good block of players," said Lopez.
He added: "It's a very difficult game, against a great team but also a direct rival. We need to win because, after the other week, we are already in the bottom half and the three points are very important.
"It's a great opportunity to beat a direct rival, to play well and prepare ourselves for the coming games."
Villarreal face German giants Bayern Munich in the group stages of the Champions League on Wednesday.
Sevilla have already been knocked out of Europe having been eliminated from the Europa League play-offs by Hannover.
Marcelino said of Villarreal ahead of the trip to El Madrigal: "They are an opponent who have very good potential, one of the best in the league, and they've kept the majority of their players for this season.
"They've lost (Santi) Cazorla, but they've made some very good signings and still have a great attacking threat, so they will be a tremendously difficult opponent. It will be a very even game and whoever commits the least errors will win."