The charity, which was founded in 1982 in the US and has 20 centres around the world, helps children with facial disfigurements such as a cleft pallet, in countries including India, Kenya, the Philippines, China and Columbia.
The charity will bring children with severe facial disfigurements to the UK for medical treatment.
American-born Ellen Agler is the executive director of the UK hub. Agler said: "Any cause that is to do with children seems to do very well here.
It is our intention to increase the number of UK medical volunteers, as well as raising funds. It costs ?xA3;500 for each child's medical treatment and we'd like to help as many children as possible."
Operation Smile spends about 5 per cent of its operating budget on overheads, allocating about 98 per cent of donations directly to programmes.
Agler said: "We need to keep the staffing pretty lean so that the bulk of the money goes directly to the programmes. We're definitely not going to become a huge bureaucracy here."
Operation Smile has rounded up a board of seven UK trustees including medical professionals, accountants and technology specialists and has acquired office space in Hammersmith, which has been donated by internet firm Netdecisions. It has set up a donor telephone line with Cambertown, a call centre management company in London.
Phil McDonald, an anaesthetist who has been volunteering for the charity abroad since it began, is head of the medical committee.
Kenyan cross-country runner and Olympic silver medallist Paul Tergat, who is taking part in the Flora London Marathon on 14 April and came second in last year's run, hopes to raise ?xA3;20,000 for the charity at a gala dinner following the event.
Last year, British grandmother Jennifer Murray, who has also become a UK trustee, took a helicopter ride around the globe to raise funds for the charity. She has also written a book about her experiences on the trip called Now Solo, with proceeds going to Operation Smile in the UK.