It happened around 10 p.m. Monday inside a hotel room along the East Freeway near Sheldon.
According to the Harris County Sheriff's Office, the boy had the gun when it went off and fired a shot into his sister's arm. She was taken to the hospital with non-life-threatening injuries.
Deputies said the shooting appeared to be accidental.
While it's early in the investigation, officials said its family violence unit will take over to determine if charges would be filed.
Both siblings were listed as runaways.