The move to separate is not a result of the ongoing payroll bungle, say the QNU.
The Queensland Nurses Union and its 42,000 members will end their affiliation with the Australian Labor Party.
QNU state secretary Gay Hawksworth said the decision to cut ties after 16 years was made by the union in February and reported to the union conference in July.
"The decision to not renew affiliation in 2011 was taken for strategic reasons, as the QNU has decided to take a different approach to its engagement with political entities, governments and the political and public policy process," Hawksworth said.
The move is not related to specific issues and was taken before the Queensland Health pay debacle in which thousands of staff were wrongly paid.
"We wanted to be placed in a position that our members understood," she said.
"Our members at times have not understood us being affiliated to one particular party and have queried us at times over the years."
Hawksworth said the QNU is the only nurses' union in the country affiliated with a political party.
"We just didn't want our members to be confused, at any time, about any actual or potential conflict," she said.
Hawksworth said the move would deprive the ALP of about $80,000 and the Left faction - which supports Premier Anna Bligh - of 12 votes on the floor of state conference.
She said the QNU would continue to use its collective strength to run industrial, community and political campaigns which promote its members' interests.
Acting Premier Paul Lucas told the ABC it was not politically damaging.
"I'm obviously disappointed that they're not renewing their affiliation but we deal with all sorts of unions whether they're affiliated or not," he said.
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