Wu Jun (now Suzhou City, Jiangsu Province). His father, Xue Kai, styled Liangwu, was a scholar at the prefectural school and was recruited as a medical officer at the Taiyiyuan during the Hongzhi era for his medical expertise, posthumously honored as the director of the institute due to his son's achievements. He was known for his remarkable accuracy in treating diseases, excelling particularly in pediatrics and surgery. Xue Ji inherited his family's medical tradition, originally specializing as a sore and wound doctor, and later became renowned in internal medicine. In 1506, Xue Ji was appointed as an academician at the Taiyiyuan; in 1511, after passing the initial external examination, he was promoted to a clerical officer; in 1514, he became an imperial physician; in 1519, he served as the vice-director of the Nanjing Taiyiyuan; and in 1530, he retired as the director of the Nanjing Taiyiyuan with the title of Fengzheng Dafu. After retiring, Xue Ji tirelessly traveled to places like Jiaxing, Siming, Xiabao, and Hengjin to practice medicine. He was diligent in his writings.

Xue Ji's works can be roughly categorized into three types. The first includes his own writings, such as Summary of Internal Medicine in 2 volumes, Essentials of Gynecology in 2 volumes, New Records from the Courtyard (also known as Golden Mirror Records of Infant Care) in 1 volume, Explorations in Surgery in 8 volumes, New Methods in Surgery in 7 volumes, Key Points of Surgery in 4 volumes, Zhengti Leiyao in 2 volumes, Kouchi Leiyao in 1 volume, Essential Mechanisms of Scrofula in 3 volumes, and Empirical Prescriptions in Surgery in 1 volume. Summary of Internal Medicine is the first work in China to name a discipline and a book title with "Internal Medicine". Essential Mechanisms of Scrofula is a monograph on leprosy; Zhengti Leiyao is a specialized book on bonesetting; Kouchi Leiyao is a monograph on oral and throat diseases, all being the earliest extant specialized literature.

The second category includes works he annotated and supplemented, such as the 24-volume Complete Effective Prescriptions for Women by Chen Zi-ming of the Song Dynasty, Essentials of Surgery in 3 volumes; the 3-volume Key to Differentiation and Treatment of Pediatric Diseases by Qian Yi of the Song Dynasty; the 1-volume Treatise on Infantile Smallpox by Chen Wen-zhong of the Song Dynasty, the 6-volume Miscellaneous Notes by Famous Physicians by Wang Lun; the 3-volume Yuanji Qiwei by Ni Wei-de; and the 20-volume Essentials of Infant Care by Xue Kai. When annotating books, Xue Ji often added his own insights and medical cases. For example, he added sections on fetal monitoring and sores and ulcers to Complete Effective Prescriptions for Women, including personal treatment experiences and formulas, and also made additions to Yuanji Qiwei.

Xue Ji emphasized the importance of the spleen, stomach, and kidney, advocating that the foundation of human health lies in the spleen and stomach. In clinical practice, he often used methods such as sweet and warm tonics to benefit the middle, and earth-tonifying and origin-strengthening techniques.