Lawes will start at six, while Mitchell and Furbank are both named among the replacements.
Mitchell will be making his England Test debut if he appears from the bench.
"We’ve had two good preparation camps in Jersey and Pennyhill Park, worked really hard and we’re ready for a tough, physical game," said England boss Eddie Jones.
"We respect Tonga greatly and we know that with props like Siegfried Fisi’ihoi and Ben Tameifuna, we are going to have to go in the front door before the back door.
"We’re especially looking forward to getting back out in front of a full crowd at Twickenham and playing some entertaining, exciting rugby for all of the supporters, we can’t wait to have them back."
Elsewhere, Dan Biggar will start for Wales against South Africa in Cardiff on Saturday (kick-off 5.30pm), despite coming off at half-time during Saints' defeat to Leicester Tigers last Saturday.
Sam Matavesi gets the nod for Fiji, starting at hooker for their clash with Spain.
Api Ratuniyarawa is among the replacements for the Flying Fijians.
England team to face Tonga: Steward; Radwan, Slade, Tuilagi, May; Farrell, Youngs; Genge, George, Sinckler; Itoje, Hill; Lawes, Underhill, Curry.
Replacements: Blamire, Marler, Stuart, Ewels, Dombrant, Mitchell, Smith, Furbank.
Wales team to face South Africa: McNicholl; Rees-Zammit, J Davies (c), Tompkins, Adams; Biggar, T Williams; Carré, Elias, Francis; Rowlands, Beard; Jenkins, Basham, Wainwright.
Replacements: Roberts, W Jones, John, Carter, S Davies, G Davies, Anscombe, L Williams.