The Owls, who currently sit third from bottom of the Championship with 18 points from 21 games, have lost their last four matches and failed to score in any of their previous five encounters.
Although despairing Wednesday fans chanted Brian Laws' name last week prior to their 1-0 defeat to local rivals Doncaster Rovers, the board decided they needed to act and sacked the former Scunthorpe boss.
And ex-Owls defender Worthington - who made more than 300 league appearances for the club - is keen on taking over at Hillsborough.
"Sheffield Wednesday is a club I was at for 11 years, so there's affection for the place there," he told BBC Sport.
"If there's a chance to have a chat then I would seriously consider it."
The former Norwich manager won promotion to the Premier League with the Canaries in 2004 and is currently awaiting news on whether he will be offered a new contract by the Irish FA.
"It's one of those situations where my contract expires with the Irish Football Association in a couple of weeks' time. We are having discussions on that," he added.
"We are between qualifying campaigns now so, as far as that is concerned, perhaps the timing would be right. If I left it would give the Association time to go and select someone else prior to the Euro 2012 qualifying round in February 2010.
"But we're nowhere near that stage at this time, I am still under contract with the Irish FA, and these are purely rumours."
Departing manager Laws had been at Wednesday since 2006 and was saddened to leave the Championship club.
In a statement released through the League Managers Association, he said:
"From my perspective it is obviously disappointing to be leaving my post as manager of Sheffield Wednesday Football Club.
"I felt that we had the nucleus of a very good side; we experienced a good pre-season and enjoyed a relatively good start to the season.
"I would like to offer my sincere thanks to all of the players and to my assistant, Russ Wilcox, first team coach, John Dungworth, and the rest of the backroom staff.
"I would also like to thank the fans for their support, Sheffield Wednesday is a brilliant club and I have enjoyed every minute of my time there."
Former Burnley boss Steve Cotterill, Exeter manager Paul Tisdale and former Peterborough chief Darren Ferguson are also believed to be in the running for the Owls job.
