Forty-five journalism and sales jobs may be lost at the Western Mail and Echo newspaper group, says a union.
The Western Mail calls itself the national newspaper of Wales
It follows other cuts which affected a sister north Wales paper, the Daily Post, also owned by Trinity Mirror.
Politicians and the National Union of Journalists asked the company to think again, and Rhondda MP Chris Bryant asked for a Competition Commission review of the newspaper market.
Trinity Mirror blamed "challenging economic conditions" for the plans.
The announcement comes two years after Trinity Mirror made a first round of cuts at the Cardiff centre with the loss of 55 jobs, 21 of which were in editorial.
It follows an unsettling time for other Welsh newspapers and media outlets.
Editorial cuts have also been threatened at the Swansea-based South Wales Evening Post, and owner Northcliffe Newspapers is considering putting the company up for sale.
Sixty seven jobs were lost when the printing press at the Evening Post's Swansea site recently closed.
Both BBC Wales and ITV Wales have also made cuts.
Martin Shipton, chief reporter of the Western Mail and an NUJ representative, said Trinity Mirror was making a profit from its Welsh publications and the announcement of potential job losses had angered staff.
"We are extremely angry about what is happening because the fact of the matter is the company, Trinity Mirror, is making enormous profits out of Wales," said Mr Shipton.
The Western Mail joined the compact trend in October 2004
"They are expecting a profit return on turnover of around 35% this year, which is an astonishingly high figure by any standards.
"Just over a year ago they relaunched the Western Mail as a compact and the sales have been going well and suddenly this comes along and it really has been extremely demoralising and people are extremely angry about it."
'Responsibility to readers'
He said circulation of the Western Mail was increasing, with about 45,000 people buying the paper daily, and feared cuts would have a negative impact on news coverage offered to readers.
"The Western Mail bills itself as being the national newspaper of Wales and there is a responsibility to the readers of Wales to ensure they get Welsh news. There is strong evidence from surveys that people want Welsh news," he added.
Trinity Mirror said: "In view of the challenging economic conditions facing all media companies Western Mail & Echo Ltd has conducted a review of its cost base.
"That review is complete, and we are now entering a period of consultation with those employees affected."
The leaders of the three opposition parties in the Welsh assembly issued a joint statement which said: "Everything must be done to ensure we continue to have a vibrant, viable newspaper industry in Wales.
"These proposals are driven by a company with both eyes on its profit margins rather than maintaining the excellence of its newspapers," said the leaders of Plaid Cymru, Conservatives and Liberal Democrats.
"These cuts will also lead to poorer coverage of local politics and community issues, and will seriously undermine local democracy and accountability.
"Trinity Mirror must abandon its plans and ensure all its Welsh titles are able to maintain the high production standards and editorial coverage for which they are widely and rightly recognised."
MP Chris Bryant tabled a Commons motion urging the company to reconsider amid Trinity Mirror's "virtual monopoly" of local newspapers, and his Rhondda colleague, AM Leighton Andrews, asked the assembly culture committee to hold an inquiry.
Mr Andrews said there were plans to merge the editorship of two local papers, the Rhondda Leader and Pontypridd Observer, and a "thriving local media industry" was important.
He told company chief executive Keith Dye of his opposition, and said: "The Rhondda Leader is owned by the Trinity Mirror group which has near-dominant position in the Welsh market.
"We need to debate the state of the press in Wales."