五四運動激發了中國知識份子的愛國熱情，為順應中國社會的潮流，東吳大學逐步進行中國化的過程。1926年首先廢除宗教必修課程，禮拜儀式亦改為學生自由參加。繼而改組校董會，三分之二的成員改由中國人擔任。1927年楊永清先生當選首任中國籍校長，訂「養天地正氣 法古今完人」為中文校訓；1929年南京國民政府正式核准東吳大學在國民政府註冊立案。 此後十年各項校務發展成果豐碩令人矚目。1930年時學校共有文、理及法三學院，十二個學系。在教學方面積極籌款推動學術研究、加強師資陣容提昇教學品質、推動師生以其專業服務社會。校園內主要建築設施均在此階段建成或動工。1930年學生人數達755人為全國基督教大學之冠。
The May Forth Movement in the 1920s and 30s aroused the patriotism in Chinese intellectuals, and Soochow University took steps to implement localization. In 1926, the mandatory religion courses were abandoned. Subsequently, the Board of Trustees was restructured, and two-thirds of its members were filled with Chinese nationals. In 1927, Dr. Yang Yung-Chin was appointed the first Chinese president. He announced that the Chinese version of the school motto, to reflect the English motto “Unto a Full Grown Man,” should be the couplet養天地正氣‧法古今完人, which in English means “Nourish the spirit of universal morality and emulate the perfect men of all ages.” In 1929, the National government in Nanjing officially approved the establishment of the school, registered as Soochow University. By 1930, the university had three colleges, the College of Liberal Arts, the College of Science and the College of Law, comprising 12 departments, and the number of students, 755, topped all those of church-established universities in China.