The Reds will face their fellow Premier League side in a two-legged tie in the New Year.
The opening game of the semi-final will be played at St Mary's in the week commencing January 9, with the return fixture set to take place at Anfield a fortnight later.
Jürgen Klopp's team booked their spot in the last four of the competition with a 2-0 home win over Leeds United on Tuesday night, having previously eliminated Burton Albion, Derby County and Tottenham Hotspur.
This is the third campaign in a row that Liverpool have reached this stage of the League Cup.