The Houston Police Department said the incident happened just before 8 p.m. in the 9800 block of I-45 north, near West Road.
Sgt. Dallas with HPD said witnesses reported seeing the man dart across the freeway, though it's unclear why.
Police said the man was hit by a white Nissan Sentra going northbound. He was pronounced dead at the scene.
HPD said the 34-year-old driver of the Nissan stayed at the scene. She was questioned and released, and it was determined she was not impaired.
The pedestrian was 46 years old, but his identity is pending verification by the medical examiner's office.
An investigation into the incident is underway.