Jacqueline Watt told a jury David Parker was innocent as she knew him "better than anyone".
The mum also recalled Parker allegedly telling her he was "babysitting" a man who was in bother – whom it later turned out to be Miss Spence.
Miss Watt was giving evidence at the trial of Parker, 38, Colin Coats, 42, Paul Smith, 47, and Philip Wade, 42, at the High Court in Glasgow.
They deny abducting, torturing and murdering Lynda Spence at a flat in Meadowfoot Road, West Kilbride, Ayrshire, between April 14-28, 2011.
Miss Watt told how she had visited Parker in prison 15 times after he had been remanded in custody in connection with the alleged killing.
Gary Allan, QC for co-accused Wade, later put it to the 38-year-old she would not want Parker convicted of murder.
Miss Watt replied: "No – because he is not guilty of it. If he was guilty of it, I would throw away the key. But he is not guilty of it – I know him."
Mr Allan said she would not know if he was guilty or not as she was not there. Miss Watt replied: "I know him better than anyone – that's what I know."
She claimed Parker had previously told her about "babysitting" a man who had been in trouble.
A report she compiled showed that in the contacts of a phone said to be Wade's, he had saved a phone attributed to Parker as "David bsitter".
Ms Mason told the court a number for Miss Spence had been saved as "madam" in a phone attributed to Coats.
Defence lawyer Derek Ogg, QC, directed the witness to another report – not compiled by her – and she confirmed a number of messages that were sent to a phone of Miss Spence's from phones attributed to John Glen.
One message read: "Don't ignore this Lynda, for your sake please."
Another message sent on April 13, 2011 read: "This is as real as it can get and you f***** him around."
The court was told another message was sent to Miss Spence's phone the following day that said: "He will chop you up Lynda at 2pm today if that 20 isn't there cash. I will help him sort you as he says it's my responsibility as I brought him in. If you don't show, no problem. I will sort things myself."
The final message the jury heard that was sent from a phone attributed to Mr Glen said she (Spence) should "get Colin to pull 20 out just now".
The trial continues.