"John McCain will speak directly to the American people about his vision for reforming Washington, getting our economy back on track and securing the peace for the next generation," Brian Rogers, a spokesman for the McCain campaign, told Reuters news agency.
"He's obviously very excited, and after the address by Governor Palin last night, we are having two mavericks at the top of the ticket."
McCain's remarks, due at around 8.30pm (02:30 GMT) follow a defiant speech by Sarah Palin, his controversial vice-presidential running mate who formally accepted the party's nomination on Wednesday.
McCain's wife, Cindy, is also due to speak on Thursday, as are Tom Ridge, the governor of Pennsylvania, and Lindsey Graham, a senator for South Carolina.
Al Jazeera's Rob Reynolds in St Paul, Minnesota, says that there is not as much pressure on McCain as there was on Palin or Obama, although the Arizona senator is expected to give a creditable and well-received speech.
And while the speech's details remain largely unknown, McCain may well go into detail about his economic policies should he be elected after both Obama and Palin were criticised for failing to do so adequately, our correspondent says.
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Palin, who was largely unknown in US politics before her nomination 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.
The governor of Alaska told delegates: "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.
"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 good people of this country."
Analysts and correspondents say the speech appeared to be well received by those at the convention, and galvanised attendees in preparation for McCain's remarks on Thursday.
Obama dismissed Palin's remarks on Thursday, saying he had "been called worse on the basketball court", and rejecting 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. Shes been through it, what, four days so far?"