Iniesta picked up a knock in last week's surprise 1-0 defeat to Switzerland and was an unused substitute in the 2-0 win over Honduras on Monday that put Spain back on track to qualify for the next phase of the tournament.
His creative flair is a key weapon in Del Bosque's armoury and his presence in the starting 11 would lift the side as they seek the victory that would set up a possible second-round clash against five-times champions Brazil or Portugal.
"Yes I think so, we are optimistic," Del Bosque said at a news conference at Spain's training base in Potchefstroom on Tuesday when asked about Iniesta's fitness.
"He has been a regular in our recent matches and always with a positive result," he added.
Spain dominated group minnows Honduras at Ellis Park on Monday but failed to convert a slew of chances, striker Fernando Torres squandering several clear opportunities on his return to the starting 11 after knee surgery.
As well as wasteful finishing, Del Bosque said he was also slightly concerned about the degree of vulnerability his team showed in the latter stages of the game.
"Yesterday's match proved more open than the Swiss game, particularly in the final half-an-hour, and up to then I thought we didn't play badly," he said.
"But I had the impression that against a stronger rival we could have turned into an easy opponent and that worries me."
Striker David Villa, who scored both Spain's goals against the Hondurans, was lucky to remain on the pitch late in the first half after he tangled with Emilio Izaguirre and slapped the defender in the face.
"I don't know what exactly happened," Del Bosque said.
"All (the players) were very aware of the fact that an incident like that, an act of stupidity, can cause a problem and can be very damaging to the team," he added.
A Fifa spokesman said it was too early to say if Villa would face disciplinary action.
"We would have to wait for the reports so it's too early for me to comment," he said.
Spain play Chile at Pretoria's Loftus Versfeld Stadium on Friday.
