The match at the Polish capital's National Stadium kicks off at 8:45 p.m. Warsaw time.
Poland are ranked 24th worldwide by football's governing body FIFA, while San Marino are last in the FIFA table, at No. 210.
The Polish team on September 5 demolished San Marino 7-1 away from home ahead of a key game against England.
Poland on September 8 drew 1-1 with England in their sixth 2022 World Cup qualifier in Warsaw.
After six rounds of fixtures, Poland are in third place in their qualifying Group I, behind England and Albania, with 11 points and a plus-11 goal differential.
The Poles will next week travel to Tirana to take on Albania in their next qualifying fixture on October 12.
Manager Paulo Sousa last month released a list of 29 players called up for the national team's October games against San Marino and Albania.
The lineup announced by Paulo Sousa includes star striker Robert Lewandowski and other well-known faces such as Napoli midfielder Piotr Zieliński and Hertha Berlin forward Krzysztof Piątek.
Piątek is returning to the squad after an injury layoff.
Meanwhile, West Ham United goalkeeper Łukasz Fabiański, who is retiring from international football, is set to make his farewell appearance for the national team on Saturday night after 15 years representing Poland.
Several other players, including defenders Arkadiusz Reca and Maciej Rybus, have succumbed to injuries and will miss the matches against San Marino and Albania, state news agency PAP reported.
Source: PAP