The South African played for Leeds United between 1994 and 1996.
Masinga was admitted into Tshepong Hospital in Klerksdorp last month and then later moved to Parktown.
Masinga was also a member of the victorious 1996 African Cup of Nations squad.
The president of the South African Football Association, Danny Jordan, said: "Sad day for South African football".
South Africa Football Association have announced the death of former striker Phil Masinga at the age of 49.
Confederation of African Football deputy secretary general‚ Anthony Baffoe‚ took to Twitter on Sunday and posted: "We have lost another hero - Phil Masinga just passed away".
He won 58 caps and scored 18 goals for his country, including the memorable strike against Congo that sent South Africa to the 1998 World Cup for the first time.
Masinga also played for Leeds in the English Premiership in the 1990's, along with Lucas Radebe.
With tributes pouring in from family, friends, Safa, supporters and former clubs such as Leeds, the details of his funeral are yet to be announced.
The former forward made 31 league appearances for Leeds, scoring five goals.
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