"We are two individuals who respect and care for each other and have made our own individual choices," Sussanne said in a statement Saturday.
The duo was dating for four years before they tied the knot Dec 20, 2000 post the success of Hrithik's debut film "Kaho Naa... Pyaar Hai". They have two sons - Hrehaan and Hridhaan.
"We are parents to two wonderful kids and our responsibility remains to protect and take care of them. Nothing can change that," said Sussanne, who is the daughter of veteran actor Sanjay Khan.
Like Hrithik, Sussanne said she would "appreciate if we are given our privacy in such a time".
"Thank you for your warmth and concern for both of us and the family," she said.
The news of their split has come just a few days before their 13th marriage anniversary, and in the midst of a medical treatment that Hrithik is undergoing at an undisclosed location abroad.
The "Krrish" star has been suffering bouts of headache. In July this year, he had undergone a brain surgery for removal of a clot at the Hinduja Hospital.
