The hospital is designed as the super tertiary care medical center in the lower northern region of Thailand.

After establishment of the Faculty of Medicine Naresuan University in 1994, the Royal Thai Government permitted a budget to build Medical Sciences building and Health Sciences Research Center inside Naresuan University to be a research and a teaching center of students in health sciences field.

The construction of Health Sciences Research Center Naresuan University was started in 1996 and completed in 2000.

On December 1, 2003, Princess Maha Chakri Sirindhorn operated the grand opening ceremony of the building and statue of Prince Mahidol Adulyadej of Songkla and the Princess Mother Srinagarindra, the father and mother of Thai public health and modern Thai medicine.

The first batch of medical students started the clinical year at Naresuan University Hospital in 2007.