Queenslanders do not understand the motivations behind unpopular decisions, Premier Campbell Newman says in the wake of his party losing the Stafford by-election.

Last night, Labor trumped the LNP in the northern Brisbane seat, with a huge swing of 18.6 per cent.

The win adds a ninth MP to Labor's ranks, with Dr Anthony Lynham securing victory over the LNP's Bob Andersen.

Mr Newman says he understands some voters are unhappy with his Government.

He admits he has made unpopular decisions but says Queenslanders do not understand the rationale behind them.

"I think the issue is that Queenslanders perhaps didn't appreciate how much of a mess the state was in, how diabolically bad the finances were," Mr Newman said.

"Nothing we have been doing has been for any other reason than to make this a better state.

"There was a big mess, strong decisions had to be taken, and indeed we've undertaken I reckon 10 years of reform crammed into two and a bit years.

"Why would a government make difficult decisions like this that clearly weren't popular if it was not ultimately in the best interests of Queenslanders?"

The by-election was forced after previous LNP member and assistant health minister Dr Chris Davis quit after several policy disagreements with the Government.

Biggest by-election swing for more than 20 years

Dr Lynham secured 61.5 per cent of the vote after preferences, in the biggest swing at a Queensland by-election since changes were made to the Electoral Act in 1992.

Congratulating Dr Lynham on his win last night, the Premier said he would be trying harder to communicate the achievements of his Government.

But he said there were no plans for a Cabinet reshuffle.

"We know that you're [Stafford voters] not happy, clearly and we're going to work extra hard to deliver on the things that we said we would," he said.

"I'd just ask people to remember that we have inherited a big mess to sort out, we had to make strong decisions."

Opposition Leader Annastacia Palaszczuk says the result is a boost for Labor in the lead-up to next year's general election and signals a warning to the Government.

"What we're seeing here in Stafford, with the way people voted here yesterday, will be symbolic of what people are feeling right across Brisbane, in Ashgrove, and right across Queensland," Ms Palaszczuk said.

"People don't want an arrogant, out-of-touch Government. They want a Government that listens, that cares about them.

"This is a Premier who is taking Queensland backwards ... he's not just not listening to people here in Stafford, he's not listening to Queenslanders right across the state."

The result comes after Labor won the Redcliffe by-election in February, with a 17.2 per cent swing against the LNP.