Wendy Martin, who ran a post office in York, said the faulty Horizon system "devastated" her health and finances.
The IT issues led to accounting errors at hundreds of UK post offices.
Earlier, MPs urged ministers to sort compensation for all sub-postmasters wrongly accused of theft.
Ms Martin, who only ran her branch for 20 months, told a public inquiry on Thursday she resorted to videoing herself cashing up, in order to show that she wasn't fiddling the figures, as the Horizon system suggested.
"My worst discrepancy one day was over £30,000," she said, adding that this was an amount she would effectively owe the Post Office. "It was awful."
The former sub-postmistress said how she called the Horizon software helpline daily as her modem continually lost connection. Ms Martin said she was repeatedly told to unplug everything and turn it on again.
She said she then noticed that accounting discrepancies would occur at the same times as the loss of connection.
At the time, she closed her branch and refused to re-open until someone from Post Office headquarters addressed the issues with her computer system. Ms Martin told how she was shouted at on the phone by a senior member of the Post Office and told to re-open, which she refused to do.
Ms Martin's witness statement came on the day a Parliamentary Committee said the government needs to work faster to make sure all sub-postmasters wrongly accused of theft receive adequate compensation.
The Business Committee has been looking at ways to speed up the compensation process, in parallel to the ongoing public inquiry into the scandal.
Unlike many others involved in the scandal she was not prosecuted, neither was her contract terminated, but Ms Martin shut the branch after deciding she was fighting a losing battle.
Describing suffering a breakdown as a result of the problems she was facing at work, Ms Martin said she "just couldn't do it anymore".
"I'd gone to a shade of grey that a human shouldn't be," she added, referring to kidney and liver issues that she suffered during her time at the branch.
She said the rumours of her stealing pushed her to the point of wearing no make-up so that "people could see how ill I looked".
Ms Martin is furious that she has lost so much financially: "I've lost my business… I'm in debt now until I'm in my mid-70s… I've lost the money I invested in my business. I've lost my retirement."
Another sub-postmaster told the inquiry he blames the Post Office for stress which led him to have a heart attack at just 33.
Mohammed Amir, from Bolton, said at the time he was otherwise healthy - a regular gym-goer, sports coach and had quit smoking.
"It's been 14 years since I had that episode - I didn't realise it was because of all this… I do blame Post Office for causing that," he told the inquiry.
Mr Amir estimated the shortfalls across his branches totalled £130,000.
"I couldn't understand why, when we'd left the office in the evening, the accounts would be different the next day. We'd be there until late in the evening, after we'd closed at half past five, trying to work out what has happened.
"I was convinced it was the system but couldn't prove it," he said.
No action was taken against Mr Amir - but he was part of the 555 sub-postmasters who won a settlement in 2019.
Between 2000 and 2014, more than 700 sub-postmasters and mistresses were accused of theft, fraud and false accounting in the most widespread miscarriage of justice in British legal history. A total of 72 have had their names cleared so far.
The inquiry is expected to run for the rest of this year. The software was developed by Japanese company Fujitsu.
The Post Office has previously said it is "sincerely sorry for the impact of the Horizon scandal on the lives of victims and their families and we are in no doubt about the human cost".
"In addressing the past, our first priority is that full, fair and final compensation is provided and we are making good progress," it added.