Sources told ESPN that the former Fulham and Portsmouth star had been diagnosed with Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease or motor neurone disease.
Diop won 65 caps for Senegal between 2001 and 2008, and was a key figure in the side that reached the World Cup quarterfinals -- one of only three African sides to reach the final eight of the competition -- in 2002.
The midfielder's close-range goal against reigning world champions set debutants Senegal on their way to one of the most famous victories in the tournament's history, and he would go on to score twice as they held Uruguay 3-3 in their final group game to reach the knockout stages.
The Teranga Lions were ultimately defeated by Turkey on the golden-goal rule in the quarterfinal.
Diop also represented Senegal at four Africa Cup of Nations tournaments, and was part of the side that reached the final in 2002, where they were defeated by Cameroon in Bamako.
At club level, he represented four English clubs after arriving in the Premier League with Fulham in 2004, and was part of the Portsmouth team that defeated Cardiff City in the 2008 FA Cup final.
Earlier in his career, he was a Swiss champion with Grasshoppers, having made the move to Swiss football and third-tier Vevey after being recognised by scouts while playing with ASC Diaraf in his homeland.
He also played for Neuchatel Xamax and spent time with Lens -- where he was a Ligue 1 runner-up in 2002 -- before making the move to English football.
After leaving Pompey for AEK Athens in 2010, he won the Greek Cup, and then returned to England to help West Ham United secure promotion to the Premier League, before finishing his career with Birmingham City.
Rufisque-born Diop, who stood at 6 foot 5, was nicknamed "The Wardrobe" due to his imposing presence in the midfield, and was named by Manchester United legend Paul Scholes as his toughest opponent earlier this year.
"FIFA is saddened to learn of the passing of Senegal legend Papa Bouba Diop. Once a World Cup hero, always a World Cup hero," the world governing body said in a statement on Twitter.