Totti will miss Sunday's game at Udinese after sustaining a hamstring injury during last week's 2-0 triumph over Napoli.
The veteran Italian striker will be sidelined for a month.
"It's not going to be easy because we know how much Totti means to Roma," said Pjanic, whose brace against Napoli handed his team its eighth straight win of the season.
"It will be a further challenge for us."
Pjanic pointed out that Roma, who lead the Serie A standings with a five-point advantage over Napoli and Juventus, has plenty of players capable of stepping in to fill the void.
"We've got a great squad with very good players," said Pjanic.
"We need to play well, even with Totti missing.
"I know (striker) Adem Ljajic has a lot of talent and is looking forward to playing on Sunday."
Ljajic is set to replace Totti and play alongside Marco Borriello and the team's top scorer Alessandro Florenzi in attack.
Pjanic is confident that the Giallorossi can keep up their impressive form.
Roma, coached by Rudi Garcia, have the best attack and the most solid defence in the competition with 22 goals scored and just one conceded.
"I think what surprises me the most is the fact that we have only given away a goal," said Pjanic. "This proves that this team is hungry and it is this that helps you to win."
Rivals Udinese would like nothing more than to end Roma's perfect start to the campaign.
However, Bianconero coach Francesco Guidolin is aware his players will have to step up their game if they are to threaten Roma.
"We are well aware that we must improve and do it quickly," said Guidolin. "Our performances are not good enough to get important results.
"We need to do better in every aspect of our game.
"I'm sure my players will have plenty of motivation to do well against Roma."
The Friuli outfit has won all of their games at home but Guidolin's men have yet to take a point on the road this season.
Last weekend's 1-0 defeat at AC Milan was their fourth loss away from home and dropped the Bianconeri to 11th place.