Ngwane was hospitalised for two weeks at the Jabulani Hospital before passing away, according to a family friend.
Kutlwano Ditsele, a film producer who works for Bomb which produces Isibaya and produced Yizo Yizo and Zone 14, took to Twitter to confirm the news.
Distele tweeted: "Rest in Peace to actor Tshepo Ngwane who was best know for his roles of Thiza in Yizo Yizo and Dr Mdu in Zone 14. May his soul rest in peace."
According to TVSA, Ngwane was "best known for his roles as Thiza in Yizo Yizo, as Mdu Sibiya in Zone 14 and as the host of the reality show RiZe Mzansi, all of which aired on SABC1."
The 39-year old Ngwane held a National Diploma in Retail Management from Wits Technikon and acted in Backstage, Tshisa,Interrogation Room and Jozi Streets.