Totti, who has scored four goals so far this season, is at 36 still Roma's key man in attack, having drawn plaudits for his renewed energy under new manager Zdenek Zeman.
The return of the 29-year-old De Rossi will be a boost to Zeman's inconsistent side who go into the game in sixth place in Serie A, two points behind Lazio.
"For us to have Daniele on the pitch is something else because we know how good he is and we know how opponents feel when he is there," defender Nicolas Burdisso told Sky Sport Italia.
"He is a symbol for us. We need the true De Rossi, who pulls us all along."
De Rossi has often been left on the bench by the Czech-born Zeman, prompting suggestions by the Italian media that he might leave the club.