The 30-year-old goalkicking second-rower has already played in two cup finals but admits time could be running out as he bids to get his hands on a first winners' medal.
Tickle was in the Hull team that lost 28-16 to St Helens at Wembley in 2008 and, before that, played for his home-town team Wigan in their 32-16 loss to Saints in Cardiff in 2004.
Now in his final year with the Black and Whites as he prepares to take up a three-year contract with Widnes, Tickle is hoping to bow out of the club on a high.
"This is definitely the biggest game in my career and possibly for many other lads," Tickle said.
"As you get older - I'm 30 now - you never know where your career is going to head.
"You've been given an opportunity and you've got to make sure that you make the best of it.
"They don't come around too often, the semi-finals of the Challenge Cup, so we'll give it our best shot.
"I've been quite lucky, I played there in 2008. It was my first visit to Wembley - I never went to the old Wembley - and it was a massive day for myself.
"I now want to finish at Hull on a high."