The 22-year-old Ospreys loose-head takes over from the injured Gethin Jenkins, who was making his 129th appearance when he captained Wales to a 27-13 win over South Africa in November.
Jenkins is out of the Six Nations with an arm injury, and will be missed said Smith.
"It's a big loss for the team to lose someone like Gethin," he said.
"But I'm happy to get the chance and to get the nod and I'm looking forward to it."
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Smith suffered his own injury frustration after making his international debut at the age of 20 against Fiji in 2014.
A torn pectoral muscle saw him slip from the radar and Scarlets' Rob Evans emerge as the player most likely to succeed Jenkins in the Wales number one shirt.
Evans has also injury problems this season, however, and will be on the bench in Rome as Smith makes his Six Nations debut.
Smith acknowledges he and Evans have an ongoing selection rivalry, but one tempered by mutual respect and a team ethic.
"I think that's the best bit about competition for places," said Smith.
"Fair play to Rob he's a great player and we push each other well.
"I know I've got the opportunity in this match but I know I'll have to give my best performance because with someone like Rob I can lose my place quite easily."
Smith came through the same Waunarlwydd RFC junior rugby set-up as outside back Liam Williams and says he is glad his junior rugby coach Tony Cleary persuaded him to give-up his ambition to be a number eight.
"I was a bit short and chubby for that," he laughed.
And Smith says he is also grateful for more wise words from a senior figure in the Wales camp.
"In the autumn Gethin was always there to help me if I had any questions," he said.
"He would be the first man to go to and he was fantastic.
"Obviously it's a bit of a loss for him not to be here n this period but I can still talk to people like Paul James back at the Ospreys and I know I can give him a call if I need any help.
"And me and Rob help each other as well.
"I know we're fighting for the same shirt, but at the end of the day we are team-mates and we can help each other out."
In the bruising, bone-against-bone world of scrummage confrontation, it seems the front-row union might be more important than selection rivalries.
Well, possibly.
Nicky Smith has big boots to fill when he wins his eighth Wales cap against Italy in Rome on Sunday.