Ronaldo has impressed on his return to Old Trafford, scoring four times in four appearances, including a goal in the clash with Young Boys in Switzerland.
The 36-year-old will now be hoping to lead his side to victory over Villarreal, who beat the 20-time English champions on penalties in the 2020-21 Europa League final.
Here, Sports Mole looks at how he has fared against the Yellow Submarine in the past.
Ronaldo has faced Villarreal on 19 occasions throughout his professional career and has a record of eight wins, nine draws and two defeats against the Spanish outfit in all competitions.
The Portugal international has found the back of the net 13 times against the Yellow Submarine, in addition to providing five assists, with all of his goal contributions coming in La Liga.
Interestingly, the attacker faced Villarreal on four occasions during his first spell at Man United, which came in the group stages of the Champions League in 2005-06 and 2008-09 respectively, with all four matches finishing goalless.
Ronaldo then played against the club 15 times in La Liga during his time at Real Madrid, scoring 13 goals, and he was only on the losing side on two occasions.
Arguably the experienced forward's finest performance against the Yellow Submarine came in September 2011, when he scored a hat-trick and provided an assist in a 4-2 success for Los Blancos at the Bernabeu.