The Everton forward is closing in on a move to the Red Devils after a fee of £75m was agreed upon by the two clubs.
Lukaku has scored 71 goals in 133 games for the Toffees.
And Hughes, who scored 163 goals for United, believes the Belgian can be the perfect replacement for Zlatan Ibrahimovic.
"It will be a different challenge for him," Hughes told Sky Sports.
"Everton are a good club - I've played at both clubs. Everton are very much a family club, United - clearly since I left - it's gone on to become even bigger on the world stage and it's a huge entity now.
"Maybe he'll find a little bit of a difference in that but his day-to-day work will be similar and I'm sure he'll be a great success there."