In an interview published today he suggests RBS chiefs could soon be based south of the Border.
Sir George declined to comment on whether there had already been a drift of key decision-making in the bank from Edinburgh to London, but said: "I do think it will be difficult for RBS in the future in terms of remaining in Scotland. It will just be more difficult."
His comments come after former RBS chief economist Jeremy Peat last week warned MSPs of a shift in the "centre of gravity" from Edinburgh to London.
Sir George, chairman of First Minister Alex Salmond's Council of Economic Advisers, also said it was "unfair" to single out former RBS chief executive Sir Fred Goodwin for criticism over the banking crisis as "many, many people" were involved. Sir George recruited Goodwin in 1998.