Coming off a bye, the two-time defending premiers are 0-2 to open their title defence while the Saints logged their first win in three games last round by holding out GWS.
With some big inclusions such as Zac Bailey and Darcy Gardiner for the Saturday lunchtime start, Lyon expected the Lions to make life tough for his team, who have lost their past seven meetings.
Brisbane will still be missing Hugh McCluggage (calf) along with suspended co-captain Harris Andrews.
The Saints called upon veteran Dougal Howard to replace hamstrung defender Anthony Caminiti while Dan Butler comes in for Hugh Boxshall (omitted).
Lyon thought the Lions should have won their opening-round match against the Western Bulldogs, who claimed a five-point thriller, and being undermanned had made it a tough task for them against Sydney.
"They were pretty good - all their data says they should have beaten the Bulldogs," Lyon said.
"The Bulldogs are great, kicked five goals from kick-ins, which is an anomaly, right, so, not too many teams are going to do that, and then Sydney at home can be really difficult and they (Brisbane) had a lot of injury and suspension.
"Gee whiz they get Zac Bailey back, Logan Morris back, they get Gardiner back, like they're a pretty good team."
Lyon said young St Kilda duo Hugo Garcia and Nasiah Wanganeen-Milera would have their hands full with Brisbane superstars Josh Dunkley, Lachie Neale and Will Ashcroft.
"Look, they're really tough in the contest and we're going to have to be tough in the contest, we're going to have to handle their stoppage work.
"They're going throw a bit at us, they're going to challenge Garcia, they're going to challenge Nas, so it's really good opportunity for us to play some really good competitive football."
Brisbane coach Chris Fagan said his players felt the "urgency" around posting their first win but thought they were tracking in the right direction.
Fagan was happy with how his side challenged the Western Bulldogs and hoped they would show more of the football they played late in their loss to Sydney two weeks ago after they were blown away in the first quarter.
"We haven't won a game at this point in time and will have to play really well," Fagan said.
"There's been no message (to the players); they know the urgency around trying to get that win on the board.
"It's not all doom and gloom, just have to build on that (second half against Sydney)."
