Cleary, who was part of the Blues side that lost the series opener in Adelaide, pulled up in pain after just 15 minutes at BlueBet Stadium and will head for scans on Monday.

Penrith are hopeful the halfback had suffered a "low-grade" strain but the setback still leaves the prized No. 7 in severe doubt to face Queensland at Suncorp Stadium on June 21.

"We're going to be without him for a while," Ivan Cleary said.

"I'm not a doctor but it's a significant injury. I think he'd be very unlikely (for game two)."

Cleary is critical to Brad Fittler's plans as the Blues fight to save the series in Brisbane for the first time in Origin history.

Fittler would likely plump for Cronulla's Nicho Hynes, who made his Origin debut from the bench on Wednesday, with Parramatta's Mitch Moses and Brisbane's Adam Reynolds possible understudies.

Cleary Snr said he had no concern picking his son after the gruelling Origin opener, claiming he had never shown signs of hamstring issues.

"When you back players up, there is always a risk," Ivan said.

"But this is the longest turnaround you can get and he showed no signs.

"I'm not sure what the issue there is."

The Panthers' coach said he'd "love" to see his son fit for Origin Game III on July 12 but added, "it's a soft-tissue injury; it's one where you can play or you can't".

Penrith's star half looked to have no signs of rust from the Origin opener when he set up winger Brian To'o with a floating cut-out pass in the 11th minute after a Zac Lomax penalty.

Just after Cleary pulled up sore, Mikaele Ravalawa crashed in at the corner for the Dragons and the Fijian winger made it a double in the 38th minute.

Jack Cogger, brought on to replace Cleary, found To'o with a pinpoint cross-field kick on the stroke of half-time, with the winger's effort converted by Stephen Crichton.

After the break, Crichton added a penalty and what followed was an end-to-end battle between the reigning premiers and the bottom-placed Dragons for the next 20 minutes.

There was another heart-in-mouth moment in that period when Penrith's NSW five-eighth Jarome Luai rolled his ankle, but he was able to play on.

The arm wrestle eventually ended when touch judge Wyatt Raymond controversially flagged for a knock-on by Dragons winger Mat Feagai which referee Chris Sutton had signalled play on.

On the next set, Sunia Turuva touched down for the Panthers.

"I saw the referee call 'Gone backwards' three times; he makes the call and then it gets changed," said interim Dragons coach Ryan Carr.

"It's a huge moment and they score off that set, but we couldn't challenge it because it was too late."

The Dragons kept going after that setback, depite losing Jack de Belin to a concussion.

Zac Lomax hit back for Carr's men but a rampaging Moses Leota put the Panthers back in control.

Crichton converted Leota's try to re-establish a six-point buffer and added a last-minute penalty to ensure the Panthers' victory.

Australian Associated Press