Rafael Benitez's men have fallen six points behind second-placed Roma in the Italian top flight, with Fiorentina closing to within three points of third spot.
But the home side, which has lost just one of its last 21 league matches on home soil, does boast a good record against the Rossoneri, having avoided defeat against Milan in the last five meetings.
Napoli has also enjoyed good form in the Coppa Italia, although that run was interrupted by a 3-2 defeat at Roma on Thursday, putting the club's chances in the two-legged semifinal in jeopardy.
Clarence Seedorf was grateful for two last-gasp goals as Milan sealed victory in its last away game - a 2-1 win at Cagliari - although that was just the club's second Serie A triumph on the road this term.
The former Netherlands international has yet to taste defeat in the league since taking over from the sacked Massimiliano Allegri. Taking seven points from the last nine available has moved Milan into 10th, six points off the European qualification places.
A 2-2 draw at San Paolo last season, sealed by Stephan El Shaarawy's double after going two goals down, sparked an impressive run of just one defeat from 19 games - going a long way to sealing the team's unlikely qualification for the Champions League.
The hero of that day will be unavailable as El Shaarawy continues to battle a foot injury.
Daniele Bonera is suspended for Seedorf's side, and Kaka is believed to be battling illness, but Benitez could welcome Valon Behrami back to action ahead of schedule after recovering from a foot operation.
- Sports & Recreation
- Rafael Benitez
- Clarence Seedorf