Hughes, who has scored eight goals this season, has picked up five yellow cards this season and will serve a one-match ban.
Ben Swallow is likely to replace Hughes, although Dominic Blizzard may also come in having played on the left wing this season.
Manager Paul Trollope also has a decision to make in attack, with striker Chris Dickson having returned to Charlton after his three-month loan deal with the Pirates expired.
Trollope is keen to add a striker to his squad in January and could make another move for Dickson, but in the meantime Darryl Duffy is likely to come into the side for the visit of Chris Hutchings' men.
Steve Jones is the only concern for Walsall. The winger is still struggling with a groin strain that has sidelined him for the past couple of weeks and he will be assessed over the next 24 hours before a decision is made on his inclusion.
Otherwise, manager Chris Hutchings has a full-strength squad at his disposal as he looks to guide his charges back to winning ways.
Skipper Mark Hughes returns to the centre of defence after serving a one-match ban in the 2-2 draw against Leyton Orient last weekend - a result which brought an end to successive defeats but saw the club lose a little ground on those around them.
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