This article explores the complex professional and personal relationship between Edward Hume, an American missionary physician, and Fu-ch’ing Yen, a Chinese physician trained in the United States, during their work at the Yale University medical mission in Changsha, Hunan, from 1906 to 1926. The partnership between Hume and Yen exemplifies the collaboration and compromise required to sustain and develop a major medical institution in provincial China, highlighting broader tensions in early twentieth-century Sino-American medical education and professional identity. Their differing priorities led to a temporary rift over the purpose of their work at the Yale mission, reflecting deeper debates about professional identity, Sino-foreign cooperation, and the evolving dynamics of Western medicine in China. Drawing on correspondence, institutional records, and contemporary reports, this study situates their partnership within broader trends of professionalisation and the localisation of scientific medicine in Republican China. It argues that the negotiation of professional status was pivotal in shaping the trajectory of their collaboration and offers insights into the local, structural, and personal dimensions of Sino-foreign cooperation in medical work.