Cook said he would fight closely with Ireland to overturn the ruling, which he said had "no basis in law or in fact".
"No one did anything wrong here and we need to stand together. Ireland is being picked on and this is unacceptable," Cook was quoted as saying by the Irish Independent.
Cook told the newspaper that bias against multinationals from the United States may have been a factor in the decision to impose the bill.
"I think that Apple was targeted here," he said. "And I think that (anti-US sentiment) is one reason why we could have been targeted."
"I think it's a desire to reallocate taxes that should be paid in the US to the EU," he added.
Cook rejected accusation by EU Competition Commissioner Margrethe Vestager that Apple paid just 0.005 percent tax in Ireland in 2014.
"They just picked a number from I don't know where," he said, adding that Apple pays 26 percent per year on its global profits.
Cook said Apple was committed to expanding its operations in Ireland despite the ruling.
"I feel like Ireland stuck with Apple when it wasn't easy to stick with Apple and now we're sticking with Ireland," he said.
In a separate interview on Thursday with Irish state broadcaster RTE, Cook said the EU decision was "maddening" and that he was very confident his appeal would succeed.