Southport, managed by former Guyana international Neil Danns, are the lowest-ranked club left in the FA Trophy, and remain unbeaten at home this season.
To reach the semi-final, Southend recorded wins against Truro City, Bath City, Chatham Town and Horsham, while Southport have knocked out two National League clubs on their route to the final four.
Southend beat Southport 1-0 in the fourth found of last season’s competition.
Maher added: “It’s the way with cup competitions; once you get through the first few rounds, the more exciting and interesting they get. So, we’re looking forward to it.”
Southend have been allocated, external 808 tickets for Southport’s Haig Avenue ground.
The other semi-final is Wealdstone v Marine.
The final at Wembley is on 17 May.