The defending European champions suffered a surprise defeat to Slovakia earlier in Group C, and they go into Friday's clash in Seville level on points with their opponents in second place.
Spain's 29-game unbeaten record at home in competitive matches means they are heavy favourites, but Del Bosque insists they must not underestimate a stubborn Ukrainian side.
"It will be a game where you have to attack, but we need balance," he said. "We have to be very careful with the threats that Ukraine have, they are good on the counter-attack.
"Ukraine have a base from Shakhtar, with good people from Dynamo Kyiv. They are a good team with a strong defensive base.
"The players know what is at stake."
Del Bosque will be without Diego Costa after the Chelsea striker withdrew due to a hamstring injury, but is confident in-form Juventus forward Alvaro Morata can step up and lead the line.
"We have trained with all the players we have, we've drawn in the position they'll play and we have many expectations for Morata," he added.
"It is good that he has become rich by going abroad. It's good to have minutes [under his belt]."
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