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.
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.