Halfpenny will miss the South Africa tour with a shoulder injury.
Byrne, 33, who plays for Clermont Auvergne in France, has not featured for Wales since 2011.
"If I was coach, Lee would have been in my Six Nations side [and] he would be a player I would have in my squad going on tour," said former Wales wing Williams.
Scarlets full-back Liam Williams replaced Halfpenny in the side which romped to a 51-3 win against Scotland on Saturday.
Shane Williamson Lee Byrne“Sometimes on these big tours you need players with experience, who have been there and done that and worn the T-shirt”
The former Ospreys full-back, who will return to Wales after signing with the Newport Gwent Dragons, won the last of his 46 caps in 2011.
Byrne has previously stated he felt his Wales career was over "a year or two ago".
Williams says Byrne's experience could prove invaluable with Halfpenny missing for the tour to South Africa.
"It is gutting for Leigh [Halfpenny] because he has been playing so well and to get this big injury and you have to feel for him," said Williams.
"Liam Williams certainly had some big boots to fill on the weekend and had a man of the match performance.
"We all know James Hook can play full back as well but sometimes on these big tours you need players with experience, who have been there and done that and worn the T-shirt.
"That is certainly Lee Byrne, and sometimes these are the players you need on tour with you to help you through tough times.
"If I was coach Lee would have been in my Six Nations side as well, a bit biased maybe, he would be a player I would have in my squad going on tour."
Wales have only beaten South Africa once back in 1999 in the opening game at the Millennium Stadium.
Williams scored a superb solo try in Wales' 37-21 defeat when the two countries last met in South Africa in 2008,
And the former Ospreys players, now playing in Japan, says Wales find the two Test tour of South Africa tough this summer with captain Sam Warburton also doubtful after dislocating his shoulder against Scotland.
"It is going to be tough," said Williams
"We all know Wales have a good enough squad to compete with South Africa physically."Certainly everyone in Wales will say no because of the results in the Six Nations.
"That is what it is in South Africa - physical. Its a tough place to go and play
"I have played there and toured their enough to know that you really have to be on top of your game to win out there.
"If the team has learnt from its mistakes in the Six Nations and have learnt what to do against the big teams to win the games, the are certainly more than capable of winning.
"It is going to be tough, there is no tougher place to play."
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