The Charity Commission has pledged to "work to minimise disruption" when a public sector strike takes places this month.
Trades unions are organising a day of action on 30 November in protest at changes to pensions.
Nigel Geary-Andrews, chair of the London branch of the Public and Commercial Services Union, which represents civil servants, said he expected the regulator to be severely disrupted because many of its employees belonged to unions.
"I should imagine most parts of the commission will be badly affected and some parts will have to close down," said Geary-Adams.
A commission spokeswoman said it was too early to say how many staff would strike and what the impact would be.
"But as with previous national industrial action we will work to minimise disruption for our customers as far as is possible," she said.
"All our guidance will be available as normal on the website and we would encourage charities to use our online services."