[1] During his 40 years in India, Hughes expanded the Welsh Mission Hospital and developed a traveling dispensary to aid those in the surrounding provinces.

[3]: 209  Hughes is best known for attempting to eradicate malaria from the area, introducing a vagus nerve resection process to alleviate pain from peptic ulcers and a rickets treatment in the infant population, recognising a protein calorie deficiency disorder called kwashiorkor in the Indian population, founding the area's first blood bank, performing the first lower segment Caesarean section without antibiotics to India, and expanding educational training for medical and nursing organisations.

Hughes then decided to pursue a career in surgical medicine and was appointed the John Rankin Fellow in Human Anatomy, as anatomical knowledge was a requirement for the first FRCS examination.

After an unsuccessful first attempt, Hughes passed the final FRCS examination in 1937, becoming a Fellow of the Royal College of Surgeons of England.

During daily life at the hospital, Hughes cared for patients suffering from road accidents, animal mauling, diphtheria, malaria, typhoid, dysentery, leprosy, and tuberculosis.

[5]: 70  Hughes was forced to return to Shillong as fighting intensified and the local hospitals were the main recipients of soldiers from the Burma Road.

[4]: 308  Due to the lack of a missionary colleague, Hughes began medical education programs for local men and women.

[2]: 67 [7] In 1947, Hughes began a travelling dispensary to make weekly visits to marketplaces around Shillong to distribute medical care and health education, which he would do for 20 years.

[2]: 68 [3]: 210 [7] Hughes developed midwifery training for local women and a maternity unit in the Mission Hospital to improve health.

While in India in 1944, Hughes was elected an elder in the Shillong branch of the Presbyterian Church, with his main responsibility being religious education.

[2]: 68 Hughes is known for performing several operations for the first time in India, such as the lower segment Caesarean section without antibiotics and vagus nerve resection process to alleviate pain from peptic ulcers.

[4]: 308 [5]: 97 [7] He also introduced ether to northeastern Indian hospitals as a form of general anaesthesia, recognised and began treating rickets in the Khasi infant population, and developed India-specific treatments for kwashiorkor, a protein calorie deficiency disorder.