The Class 9 student told her teachers that in the early hours of the morning, the founder of the orphanage would call her to his room and abuse her.
Hyderabad police has registered a complaint and the girl has been shifted to a government home in Nimboliadda area.
Police are on the lookout for Jadi Madhav, the founder of the orphanage Aadarana.
A few weeks ago, a girl at another orphanage in the city alleged sexual assault by the man who runs it.
Child rights activist Achyut Rao, who is a former member of the Telangana State Commission for Protection of Child Rights, said the negligent attitude of the Women and Child Welfare Department is leading to such cases. "Aadarana should be merged with the government home. Other private orphanages should be thoroughly inspected to ensure there is no wrongdoing and children's rights are protected,'' Mr Rao said.
In April this year, a video that shows a group of teenage girls from a Hyderabad orphanage, with around 200 children, clearing a manhole around their hostel emerged. The officials who run the orphanage were booked.
In March, another case of child labour had come to light, when a teacher of a government school in the states Ranga Reddy district forced students to work. For nearly a month, students at Shivarampally ZP High School toiled to demolish an old compound wall.