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29 August 2018, 18:30 | Updated: 29 August 2018, 18:33
Robson-Kanu announced his international retirement on social media as Wales manager Ryan Giggs announced his squad for next month's Nations League games against the Republic of Ireland and Denmark.
"I am grateful to have lived a dream in representing my nation at an international level," Robson-Kanu wrote on social media.
"It has been an honour to pull on a shirt supported by true pride and unrivalled passion.
"I have made the decision to retire from international football.
"Long thought, but a decision made; commitments to my family and dedicating what time I have available to them and choosing to focus on my club career within sport and time needed away from the game.
"I wish Ryan Giggs and the team continued success in the years to come, and appreciate his understanding and support, a new generation to continue building on what Gary Speed and Chris Coleman have set in place."
Robson-Kanu was capped by England at under-19 and under-20 level, but qualified for Wales through his Caerphilly-born grandparents and went on to make 44 appearances for his adopted country.
The 29-year-old West Brom striker scored five times and will forever be remembered in Welsh football for his 'Cruyff turn' goal in the 3-1 Euro 2016 quarter-final victory over Belgium.
Giggs said: "I spoke to him yesterday and it was a difficult decision for him.
"He's had a difficult six months, with the birth of his baby, and he wants to focus on his family and his club career.
"He's an icon in Welsh football with the goal he scored against Belgium and I wish him all the best."
Newcastle defender Paul Dummett was named in Giggs' 25-man squad after choosing to end his international exile.
Dummett told Giggs' predecessor Coleman in May 2017 that he did not want to be considered for Wales duty to focus solely on his club career.
The 26-year-old reiterated that message to Giggs after his appointment in January, but Dummett now returns to the squad with Aston Villa left-back Neil Taylor dropping out.
Dummett is now keen to add to his two caps with Giggs saying: "It is a boost. I spoke to Paul when I took over and he wanted to focus on Newcastle at the time.
"But I've had a chat with Paul and he's in a good place now.
"He's playing regularly and captained his boyhood club on the weekend. I'm looking forward to working with him."
Ashley Williams, 34 last week, retains the captaincy despite his difficulties at club level.
Williams has been sent off twice in his last three league starts, but Giggs believes he will get a new lease of life after leaving Everton and joining Sky Bet Championship club Stoke on loan.
"Ash has been fantastic since I took over, leader on and off the pitch," Giggs said.
"Nothing's changed in that respect and it's good to see him playing regular now at Stoke."