Lauri Love, who has Asperger's syndrome, worries he will be sentenced to up to 99 years.
"If I went into a US prison, I don't think I'd leave again," he told the BBC's Victoria Derbyshire programme.
A judge will announce next week whether Mr Love, from Stradishall, Suffolk, should be extradited.
Mr Love, who could face trials in three different US states, is accused of hacking into the FBI, the US central bank and the country's missile defence agency.
He said the US prison system was "poor" at handling people with psychological conditions, who faced widespread bullying.
"The way that mental health is dealt with in America is not in any way therapeutic," he said. "I have Asperger's and I have depression, so suicide is a real risk.
"And if I get a 99-year sentence, it's an absurd length of time, meaning I would die in prison anyway."
Mr Love calculates this could be the total combined sentence length if he is found guilty of hacking offences in each of New Jersey, Virginia and New York.
The Federal Bureau of Prisons says it works to provide education to staff and inmates on suicide prevention.
Mr Love told Victoria Derbyshire he could be "bullied" into accepting a plea bargain in the US - receiving a shorter sentence in return for admitting one or more of the alleged offences.
"The threat of what might happen to me is always in the background," he said. "I've been scratching my face as a nervous reaction, which has exacerbated my eczema."
Mr Love, 31, was first arrested at home in 2013 and had computer equipment seized by British police, who then released him on bail.
He was not charged in the UK, where the investigation into him was dropped.
In England and Wales, the maximum sentence for a computer crime such as those of which Mr Love is accused is two years and eight months.
His defence team argues that his depression and Asperger's syndrome - a form of autism - mean he should not be sent abroad, but US prosecutors say he is using his mental health issues as an excuse to escape justice.
"That's offensive to me, as someone who has had problems with mental health for all of my life," Mr Love said. "I really feel for my parents, who have the worry and the stress of this. It's been very difficult for them."
In 2012. the then Home Secretary, Theresa May,  blocked the extradition to the US of Gary McKinnon, a UK hacker with mental health issue, saying he was a suicide risk.
Since then, the law has changed, so judges rather than politicians decide on extraditions.
Mr Love's case is regarded as the first real test of the new law.
A judge at Westminster Magistrates' Court will announce her decision on whether to extradite Mr Love on 16 September.
Mr Love said he was "guardedly optimistic" he would be allowed to remain in the UK.
The Victoria Derbyshire programme is broadcast on weekdays between 09:00 and 11:00 on BBC Two and the BBC News channel.

The Airlander 10 - part plane, part airship - was due to take off from Cardington Airfield in Bedfordshire on Sunday.
The aircraft measures 302ft (92m) long and is about 50ft (15m) longer than the biggest passenger jets.
It is not known when another attempt at a test flight will be made.
Christened the Martha Gwyn, the Â£25m aircraft can only fly in daylight for a test flight and it was feared the flight would not have been completed before dark by the time the issue was resolved, an organiser said.
It was first developed for the US government as a surveillance aircraft but the project was shelved amid defence cutbacks.
British firm Hybrid Air Vehicles (HAV) launched a campaign to return the Airlander 10 to the skies in May 2015.
The huge aircraft will be able to stay airborne for around five days during manned flights.
HAV claims it could be used for a variety of functions such as surveillance, communications, delivering aid and even passenger travel.
A British man wanted in the US for allegedly hacking into government computers says he fears dying in jail if he is extradited.
[NEXT_CONCEPT]
The maiden flight of the world's longest aircraft has been postponed at the last minute because of a "technical issue".