The Ted actor will host the Oscars for the very first time at the 85th annual ceremony, following on from this year's presenter Billy Crystal.
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MacFarlane addressed the pressures of helming the movie industry's biggest night while speaking to UCLA students earlier this week.
"The people who have not done well, I would classify every single one of them as a noble failure, as an honorable failure, because at least they were trying something new," the comedian said, reports Entertainment Weekly.
He went on to say: "[David] Letterman was not well received when he hosted the Oscars [in 1995]. But I loved it. I remember watching that and thinking, 'He's doing something fresh', which is always a good thing.
"That's going to be the challenge. And if I can do it without torpedoing my career and getting drummed out of the business... then that would be good, too. All I can do is work my very best."
The star then joked: "That's a lame f**king answer. Sorry!"
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MacFarlane previously commented that he is both "ecstatic" and "surprised" to have been asked to host the Oscars.
"I have done a fair amount of hosting in the past but nothing of this magnitude. I was very, very pleasantly surprised," he said in October.
The 2013 Oscars will take place at the Dolby Theatre at the Hollywood & Highland Center in LA and be broadcast live on ABC.
Watch a trailer for MacFarlane's Ted below:
