Boxing SA director of operations Loyiso Mtya said the left-handed boxer from Scenery Park was stabbed to death on Saturday night by someone he knew.
Mtya said he was told that a known person stormed into Madondile's home and stabbed him.
"I was told he died in his shack," said Mtya.
Madondile's death is the latest in a barrage of blows to South African boxing this year.
The sport has also lost veteran matchmaker Moss "Lord Mayor" Tau, world-class ring official Isaac Tshabalala, promoter Korda Manqina, manager Magali Botha, boxers Malibongwe Thoba, Galelekile Magabi and Corrie Sanders, as well as writer Junior Motsei.
Madondile, 30, was part of the Eyethu Boxing Gym, owned by trainer-manager Mzimasi Mnguni.
"I'm at a loss for words," said Mnguni. "Madondile had just qualified to challenge reigning South African junior featherweight champion Macbute Sinyabi. I was going to stage that fight on December 8."
The boxer, who was rated No 6 in the country, shocked the boxing fraternity by stopping talented Jerome Cebekhulu from Durban in the second round at Mdantsane Indoor Centre on October 21.