The regulator’s budget will fall from £29.3m in the current financial year to £21.3m by 2014/15, the government announced in this week’s spending review.
Jack Papasavva, negotiations officer at the PCS with responsibility for the Charity Commission, said it would "simply not be able to function with a further reduction in resource".
He said: "Quite apart from the disastrous impact on our members’ livelihoods, fewer staff will inevitably result in poorer regulation of the sector.
"Without proper funding of a strong and independent regulator, the government’s big society programme may push more and more public services and money into voluntary sector bodies that are left virtually unregulated and unsupervised."
About 60 per cent of the commission’s 400 staff are members of the union.
Dame Suzi Leather, chair of the commission, said in a statement after the budget announcement was made that the regulator was disappointed with an "extremely challenging settlement".
She said the regulator would need to make significant changes to the way in which it engaged with charities and the public as well as the scope of its regulatory activity.