Guardiola’s side faces a side that knocked league leaders Liverpool out in the last round and City will need to be careful not to slip up like the Reds.
With little chance of winning the league, City will likely go all out in the FA Cup as they chase their last shot at silverware.
The Spanish head coach firstly skipped questions on the news that La Liga president Javier Tebas has reported Manchester City to the European Commission for alleged breaches of rules relating to state-owned companies.
Eventually, he was asked whether Plymouth was an unknown in the competition and referred to their victory against Liverpool.
"It is not unknown. If you are able to beat the best team in the country this season, Liverpool. They went unbeaten also at Brentford then it is not unknown."
He was then questioned on whether talented youngster Oscar Bobb is ready to return from injury after he had a promising pre-season, only to suffer a broken leg on the eve of the campaign.
"He is getting better training yesterday and today as well but have been (out) longer than we expect but hopefully he can finish his part and can help us in the last part of the season. We want to help him desperately.
"It is a tough period for him but always there is light at the end of the tunnel. Always has been like that in life - sport especially."
The City boss then said that new signing Vitor Reis was in contention to start and stated that he is a long-term player that he is pleased with how he is adapting at the club so far.
"He is young, he came from Brazil. He has incredible focus. Defenders there have great physicality and conditioning, but also are so clever and intelligent, and this is one of the ones. He does not come for a short period, he comes for a long, long time.
"We are really pleased for the way he is training and behaving and the potential that he has."
One journalist did get an answer to the wider question of why Manchester City are a target for other people such as Tebas despite Guardiola avoiding the subject earlier.
"I don't know. It happened in the past with UEFA and in a few weeks it'll happen in the Premier League, the sentence (to the 115 charges), right? We wait, and after we talk."
Guardiola then spoke on the club's recent success and whether older players such as Kevin De Bruyne will be part of their future once the season ends.
"Never impossible but it is difficult because when you have done what we have done it was deemed impossible before we did what we have done. There are players here that their age is over 30 but they are part of the future of this club.
"Except Kevin (de Bruyne), and Kevin and the club will decide on his future everyone who has a contract for next season I expect him to be here.
"They are going to help us. Next season will be a lot of games. We cannot do it just with our new ones. They will be able to help and be part of our season."