Hughes made his full international debut aged 18 in 1998 and has earned 112 caps for Northern Ireland, the third most in the nation's history, behind Steven Davis and goalkeeper Pat Jennings.

He made his first team debut in the Camp Nou in a match between Newcastle and Barcelona on 26 November 1997, replacing Philippe Albert at half-time in a 1–0 UEFA Champions League defeat.

[17] He scored his first goal for Fulham on 26 December 2010, heading a Simon Davies cross to open a 1–3 defeat to West Ham United at Craven Cottage.

[20] He scored his third goal for Fulham, in his third different competition, against Manchester United in the fourth round of the FA Cup on 26 January 2013, heading Giorgos Karagounis' cross at the end of a 4–1 defeat at Old Trafford.

Manager Harry Redknapp signed him on a short-term deal until the end of the season, saying that Hughes would be useful in a defence suffering from injuries, while the player himself refuted suggestion that he was taking a step down in his career.

On 24 May, Hughes was an unused substitute as QPR earned promotion to the Premier League with a 1–0 victory over Derby County in the play-off final at Wembley.

[30] He made his debut eight days later in a 0–3 home loss to Western Sydney Wanderers at the Melbourne Rectangular Stadium, being replaced at half time by Jack Clisby.

[31] On 2 January 2016, Hughes scored his first goal in Australia, heading in Harry Novillo's corner kick to open a 2–2 home draw against Sydney FC.

[38] Hughes signed for Scottish Premiership club Heart of Midlothian on 9 January 2017, agreeing a contract due to run until the end of the season.

[39] He made his debut 13 days later in a Scottish Cup fourth round match away to Raith Rovers, in which BBC Sport described him as having "the composure of a Northern Ireland centurion despite his advancing years".

With Hughes injured, Fulham teammate Chris Baird was given the honour of captaining Northern Ireland for Nigel Worthington's first games as manager.

Hughes scored his only international goal, thirteen and a half years and 77 caps after his debut, against the Faroe Islands on 10 August 2011, opening a 4–0 win in qualification for UEFA Euro 2012 at Windsor Park.

[44] On 19 February 2012, Hughes announced his return to international football,[45] and ten days later played in Michael O'Neill's first match as manager, a 3–0 home friendly defeat to Norway.

[27] Ahead of UEFA Euro 2016, Hughes became the first Northern Irish outfield player to earn 100 caps when he came on as a 30th-minute substitute for the injured Craig Cathcart in a goalless friendly away to Slovakia on 4 June.