On their 22nd appearance at the continental fiesta, Kwesi Appiah's men are hoping to beat 23 other teams in the June 21-July 19 tournament in Egypt.
“Defensively we need experience, it's very important," five-time Afcon participant Paintsil told TV3 Sports.
"Without experienced defenders, there is going to be a lot of problems.
"But for me, Jonathan Mensah [and] John Boye being there, I think we are good to go.”
Ghana have been drawn against defending champions Cameroon, Benin and Guinea-Bissau in Group F.
“The back four is important for the team, playing left back and right back is important," Paintsil added.
"Can they communicate together? Do they recover when one is off? Are they okay in the air? It's important."
Mensah and Boye will be making their fifth and sixth appearances, respectively, at the Afcon finals. The former has also played at two World Cups while the latter made his debut at the global showpiece in 2014, when the Black Stars last played at the event.
Four-time champions Ghana finished fourth at the 2017 Afcon in Gabon.