The UN children's agency said the conflict in central Kasai has disrupted food supplies and undermined medical facilities.
The crisis has left almost 400,000 children "at risk of severe acute malnutrition", a statement said, meaning they could die without immediate aid.
UNICEF "needs USD 40.2 million for its urgent response" to the situation, the statement added.
"Without adequate medical help, without access to food and drinking water, the lives of hundreds of thousands of children are under threat."
The fighting erupted after government troops last August killed tribal chief Jean Pierre Mpandi, also known as Kamwina Nsapu, who had launched an uprising against President Joseph Kabila.
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