The 27-year-old, who has suffered a string of injuries over the past few seasons, starts at 12 in the absence of injured Ben Te'o.
Elliot Daly is preferred at full-back to Mike Brown, who is left out of the 23-strong matchday squad.
George Kruis partners fellow Saracen Maro Itoje in the second row.
Owen Farrell starts at fly-half, with Henry Slade partnering Tuilagi in midfield and George Ford on the bench, while flankers Tom Curry and Mark Wilson make their first Six Nations appearances.
