Repsol Honda rider Marquez holds a 13-point lead going into the final race of the season as he and defending champion Lorenzo go head to head for the world title.
Factory Yamaha rider Lorenzo has won the last two races to take the battle for the championship to the final day but Marquez is still favourite to add the MotoGP crown to his Moto2 and 125cc world titles.
Marquez has good memories of Valencia after starting from the back of the grid in last season's Moto2 race but still finishing first.
He has spent the time since the last race at Motegi in Japan, where he finished runner-up to Lorenzo, recovering from a neck injury he suffered in a practice crash.
Marquez said: "After my accident in Motegi I've been doing muscular rehabilitation on my neck in anticipation for the race, and it now feels much better.
"We've had good races in Valencia; I've always tried to give it my best there. I have fond memories of last year's race in Moto2 but the weather will also be a factor to consider because it is very changeable.
"I'm already looking forward to getting back in the pit garage and getting on the bike.
"Obviously we know what is at stake in this final Grand Prix of the year, but we will - as ever - approach it as we have done every other race, and work hard from the Friday and do our best."
While the main focus will be on the MotoGP race at Valencia the battle for the Moto3 world title is set to be an exciting one as three Spanish riders go into the final race of the season with a good chance of lifting the crown.
Luis Salom holds a two-point lead over Maverick Vinales while Alex Rins is only three points further back.
The three riders, who all race for KTM, will be looking to prove they are the next hot property to come out of Spain.