The Capital One Cup holders won their opening Europa League group game 3-0 against Spanish giants Valencia, though should face an easier task against the visiting Swiss side
The Premier League side began their Group A campaign with a comprehensive 3-0 victory at the Mestalla, but have failed to win in their last two home games against Liverpool and Arsenal.
Indeed, Swansea's last victory at the Liberty Stadium came in the Europa League play-off against Petrolul Ploiesti in August, when they demolished the Romanian side 5-1 to confirm their place the group stages.
Michael Laudrup's team scored nine goals in their two qualifying matches at home though and, after their result in Spain, they are sure to be high on confidence going into this clash.
Forwards Wilfried Bony and Michu were both on the scoresheet at the Liga club, but St. Gallen have a threat of their own in attack.
Striker Goran Karanovic - who joined during the close-season - has scored eight goals in 13 appearances this season.
And his form is a major reason why the Swiss outfit arrive in Wales on the back of a 12-game unbeaten in all competitions.
St. Gallen also won their opening Group A match - against Kuban Krasnodar - and, like Swansea, will want to maintain their 100 per cent record.
Jeff Saibene's side sit four points behind leaders Basel in the Swiss Super League with a game in hand, and have the second meanest defence in the division having only conceding seven in nine games.
Swansea have four players unavailable for the game, with Gary Monk (knee), Angel Rangel (ankle), Ashley Williams (ankle) and Pablo Hernandez (hamstring) all sidelined.
Sven Lehmann is the latest St. Gallen player to be ruled out - the young striker broke his leg last week - with Ilija Ivic and Dzengis Cavusevic both long-term casualties.