The 31-year-old defender hopes the decision will prolong his club career with Premier League side Fulham.
"After thinking long and hard, I have decided to retire from international football after the final two Euro 2012 qualifiers, to concentrate on my club career and hopefully prolong it for another few years," said Hughes.
"I have always felt very proud and privileged to play for my country and it has also been a great honour to captain the side. It has not been an easy decision, however, after speaking with players, managers and my family, I knew it was the right time to call it a day. I also knew in my own head it was the right time.
"I would like to thank everyone for their support over the years - managers, players, fans and my family. I have played under some great managers and have enjoyed every minute playing for Northern Ireland and hopefully we can get a good finish to the Euro 2012 campaign."
Northern Ireland, who currently occupy fifth place in Group C, still have a slim chance of progressing to next year's tournament and they next face Estonia on Friday, October 2 2011.