The Chairperson of the Senate Intelligence Committee, Diane Feinstein, repeatedly appealed to the protesters not to interrupt the hearing.
But the protesters, spread out in the chamber, rose one by one, raising slogans and waving placard that Brennan is a security risk. One of the demonstrators held a sign saying "Brennan = Drone Killings".
The chairperson then recessed the proceedings as security personnel cleared the protesters from the room.
After the resumption and his introduction as a CIA vetran, Brennan told the protest-disrupted hearing the United States remains at war with al-Qaeda and other terrorists and is under ‘daily cyberattack’ by foreign countries and others.
In a statement delivered before he answered questions, Brennan promised to keep members of the congressional intelligence committees ‘fully and currently informed’ and acknowledged that the CIA "is not immune from scrutiny" of its efforts to safeguard the nation.
The shouted protests centered on CIA drone strikes that have killed three American citizens and an unknown number of foreigners overseas.
It was a topic very much on the mind of the members of the Senate Intelligence Committee who eventually will vote on Brennan's confirmation.
In the hours before the hearing began, President Barack Obama ordered that a classified paper outlining the legal rationale for striking at US citizens be made available for members of the House and Senate intelligence panels to read.
It was an attempt to clear the way for Brennan's approval, given hints from some lawmakers that they might hold up confirmation unless they had access to the material.
In his opening statement, Brennan said, "The need for accurate intelligence and prescient analysis from CIA has never been greater than it is in 2013 — or that it will be in the coming years."
He said historic transformations continue sweeping through the Middle East and North Africa, with "major implications for our interests, Israel's security, our Arab partners and the prospects for peace and stability throughout the region."
Additionally, Iran and North Korea "remain bent on pursuing nuclear weapons and intercontinental ballistic missile delivery systems," he noted.
He said the United States remains at war with al-Qaeda and its associated forces, which he said seek to "carry out deadly strikes against our homeland and our citizens as well as against our friends."
As for US computer systems, he said they are under daily attack by "nation states, international criminal organizations, subnational groups and individual hackers."
Brennan is a veteran of more than three decades in intelligence work, and most recently served as Obama's top counter-terrorism adviser in the White House. Any thought he had of becoming CIA director four years ago vanished amid questions of the role he played at the CIA when the Bush administration approved waterboarding and other forms of "enhanced interrogation" of suspected terrorists.
White House spokesman Jay Carney said Wednesday the White House is making "extraordinary accommodation" in allowing lawmakers to view classified Justice Department legal advice on drone strikes against Americans. Carney said the White House does not plan to send the Justice memos to lawmakers beyond those on the House and Senate intelligence committees.