The Cambridge University medical student, 29, left Blues for Racing 92 in 2013 and joined Quins this season.
He was preparing for the Varsity match when Quins posted a bonus-point win at Cardiff Arms Park in November.
"If you're playing against Jamie, you make your tackles," said Wilson.
Roberts was British and Irish Lions man of the series in their 2-1 Test defeat by South Africa in 2009.
The 6ft 4in, 17st 4lb centre also starred as the Lions beat Australia 2-1 in 2013 in a career that has seen him win 74 Wales caps.
"It'll be great for the players to shake hands and catch up with him before and after the game, but during the game it's business as usual."
Quins also recruited former Ospreys and Wales tight-head prop Adam Jones from Blues before the 2015-16 campaign.
Wilson added: "Our boys will be extremely motivated with a few links there, Adam Jones as well from last year."
Harlequins have four bonus-point wins and need only a point from the encounter at the Stoop to top the group.
They took the extra point in the last minute at the Arms Park, with a try from Danny Care thwarting Blues' hopes of a dramatic late win.
"It's obviously a huge challenge to go to Harlequins and get a win in front of their home crowd, but the boys want to put right the performance at home against a Harlequins side that deserved the win," said Wilson.
"Since then we've improved out performances with four wins out of five."
Blues had a weekend off before the match with the postponement of their fixture against Munster, while Harlequins inflicted a first Premiership defeat of the season on Saracens.
Wilson believes the the break will have benefited his side and they will travel "with confidence that we've played some good rugby to get the results we've had recently".
He added: "If we can perform to that level, we can cause Harlequins a headache."
Wales captain Sam Warburton, fellow flanker Ellis Jenkins and Wales full-back-fly-half Gareth Anscombe could all return from injury for Blues.

Gunmen stormed the al-Jawhara shopping centre in Baghdad al-Jadida on Monday evening, after setting off a car bomb.
When security forces stormed the building, two assailants detonated explosive belts, while two others were shot dead, police sources say.
At the same time, 20 people died when two bombs exploded north of Baghdad.
Security sources said an improvised explosive device was detonated at a tea shop in the town of Muqdadiya, which is some 80km (50 miles) from the capital.
A second device blew up as medics rushed to the scene to treat the wounded.
Later, five civilians were killed when a car bomb exploded in exploded in the south-eastern Baghdad suburb of Nahrawan, police and medics say.
There was no immediate claim of responsibility for the bombings in Muqdadiya and Nahrawan, but IS said in a statement posted online that it was behind the attack on the Baghdad shopping centre, which is located in a predominantly Shia district.
The Sunni Muslim jihadist group, which controls large swathes of northern and western Iraq, said it had targeted "rejectionist heathens" - its derogatory term for Shia.
Seven people, including two policemen, were killed by the car bomb blast at the start of the attack, police and medics told the Reuters news agency.
Another five were shot dead as the militants stormed the building, while six died when two of the assailants detonated their explosive vests, the sources said.
Interior ministry spokesman Brigadier General Saad Maan denied initial reports that people had been held hostage by the militants, according to Reuters.
An interior ministry source meanwhile told the BBC that several attackers might have escaped, contradicting a claim by a police source that four had been arrested.
Cardiff Blues' tackling will have to be up to the mark against Harlequins' Wales star Jamie Roberts in their European Challenge Cup away match on Sunday, says head coach Danny Wilson.
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The jihadist group Islamic State (IS) says it targeted Shia Muslims in an attack on a Baghdad shopping centre, which reportedly killed 18 people.