Khan and his Tehreek-e-Insaaf (PTI) or Movement for Justice party, along with British and American activists, plan to drive en masse more than 200 miles (320 kilometres) from the capital Islamabad to South Waziristan.
But the government says Taliban bombers intend to attack the rally and local authorities say foreigners will not be allowed to enter Pakistan's tribal belt, considered a Taliban and al-Qaida stronghold on the Afghan border.
Missiles fired by unmanned US drones routinely target militants operating in the semi-autonomous area in what US officials say is a key weapon in the war on terror.
Peace campaigners condemn the strikes as a violation of international law, Pakistanis as a violation of sovereignty that breeds extremism, and politicians including Khan as a sign of a government complicit in killing its own people.
Khan, a vocal critic of the US-led war on terror who is campaigning ahead of a general election next year, says he wants to show the world the damage inflicted on innocent people by the drone campaign.
"The collateral damage - people's women and children getting killed have created militants and multiplied militants," he said. "This is the only time ever in history that a country has been bombed by its own ally."
He plans to travel with 30 American anti-drone campaigners from the group Code Pink and the British head of legal lobby organisation Reprieve, Clive Stafford Smith.
Critics accuse the former cricketer of blatant electioneering and of ignoring both atrocities blamed on Islamist militants and abuses by the Pakistani army.
Over the last year, Khan has become a growing force in politics, challenging the feudal and industrial elites who traditionally dominate in Pakistan, but there is scepticism about his ability to translate popularity into seats.
The PTI plan to drive to the edge of the tribal belt on Saturday and to Kotkai village in South Waziristan on Sunday to hold a demonstration.
Khan says that if the authorities intervene, they will hold the gathering wherever they are stopped.
He and his supporters have brushed aside fears that their convoy could be attacked by Taliban and other Islamist militants.
Pakistani Taliban spokesman Ehsanullah Ehsan put out a statement on the eve of the march, denying reports that they had promised to provide Khan with security.
"Our mujahideen are not so priceless that we deploy them to protect a Westernised and secular personality," Ehsanullah said.
The umbrella faction said it had no need for "sympathy" from a "secular and liberal person" trying to increase his political stature.
Stafford Smith has written to US President Barack Obama asking him not to order a drone strike on the protest.
Although leaked US cables have revealed tacit support for the drone strikes from Pakistan's military and civilian leaders, Islamabad has increasingly condemned the programme as relations with Washington have deteriorated.
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The Pakistani government argues that the attacks are unacceptable violations of its sovereignty and wants to be given the technology to carry out the operations itself.
A report commissioned by Reprieve, Stanford Law School and the New York University School of Law last month gave a devastating account of the affect that drone strikes have on ordinary people.
It said the strikes terrorise civilians, damage US credibility, work as a recruitment tool for militants and generally kill low-ranking fighters.
Reliable casualty figures are difficult to obtain but the report estimated that 474 to 881 civilians were among 2,562 to 3,325 people killed by drones in Pakistan between June 2004 and September 2012.
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Edited By Cen Fox Post Team
