Messi scored as Barcelona beat Napoli 3-1 on the night (4-2 on aggregate) to secure a place in the Champions League quarter-finals.
But the Argentine forward had a goal ruled out by VAR after he was adjudged to have handled the ball during the build-up to his effort.
He thought he had bagged his second goal of the night until Cakir overturned the decision through the help of video review.
And the Barcelona skipper held it against the Turkish referee as he declined to shake his hand following the full-time whistle.
A frustrated Messi wagged his finger at the match official before walking away.
Messi’s interaction with Caki sent social media wild.
One Twitter user wrote: “That’s the same ref who called that joke of a penalty on Mascherano in 2018 World Cup that almost cost Argentina a spot in knockout stages. Luckily Argentina scored late and advanced anyway, but Messi doesn’t forget!”
A second tweeted: “It’s like he has an agenda against Messi, the fact that he also had to spend 5 minutes checking that stone wall penalty on Messi is disgraceful.”
A surprised user added: “Didn’t see that coming.”
Meanwhile, Barcelona face Bayern Munich in the quarter-finals.
The German champions smashed Chelsea 7-1 on aggregate to earn their spot in the last eight of the competition.