And in a further blow to Wales' back three options, Blues star Leigh Halfpenny has also been ruled out of the series with an ankle injury.
But Hook is ready to live up to the unwanted tag of 'utility back' by filling the gap again.
"It's the same scenario as last year when Lee was injured and I was thrown in the deep with not much experience of the position," said Hook.
"I'll play there again if I'm called and at least I've got two weeks training to get used to it this time."
Hook featured at full back this time last season due to another injury to Byrne but was then moved into the centre by both club and country.
The 25-year-old was a sensational success at 12 and 13, producing a series of brilliant displays as the Ospreys claimed a third Magners League crown.
Much has been made of his positional switches but Hook insists that representing his country is a massive honour wherever he is selected.
"Being shifted around is a little unsettling but it's something I have dealt with,2 added Hook.
"I just look back a couple of years when I was on the bench most of the time and that was a lot more frustrating.
"I'm happy as long as I'm playing for Wales, if that's outside-half, centre or full-back."
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