Al Jazeera's Rob Reynolds in St Paul said McCain would be clearly aiming in his speech to show the party he was still a "maverick", as he often claims, but also that he can still keep the party's conservatives on side.
McCain's remarks, due at around 8:30pm on Thursday (02:30 GMT Friday) follow an aggressive speech by Sarah Palin, his controversial vice-presidential running mate who formally accepted the party's nomination on Wednesday.
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Palin, who was largely unknown in US national politics before being selected by McCain last week, has faced a storm of criticism over her unmarried teenage daughter's pregnancy, her alleged role in the sacking of an Alaskan official and questions about her political record.
Palin's anti-abortion and pro-gun background has also provoked controversy.
However on Wednesday the Alaska governor condemned what she called the "Washington elite" for being out of touch with the plight of US citizens, as she made history by becoming the first woman to be nominated for the post by the Republican party.
"I've learnt quickly these past few days that if you're not a member in good standing of the Washington elite, then some in the media consider a candidate unqualified for that reason alone," the governor of Alaska told delegates.
"But here's a little news flash for those reporters and commentators: I'm not going to Washington to seek their good opinion. - I'm going to Washington to serve the people of this great country."
Analysts and correspondents said the speech appeared to be well received by those at the convention, and galvanised attendees in preparation for McCain's remarks on Thursday.
But Obama dismissed Palin's remarks on Thursday, saying he had "been called worse on the basketball court".
He also rejected Republican claims that criticism of Palin had been sexist.
"I assume that she wants to be treated the same way that guys want to be treated, which means that their records are under scrutiny," he said.
"I've been under this for 19 months. She's been through it, what, four days so far?"