Research-oriented universities are an important decisive force for national and regional scientific and technological innovation and high-quality economic development .Under the background of innovation-driven development strategy and the high-quality integrated development of the Yangtze River Delta, based on the knowledge production function and performance evaluation theory, the DEA- Malmquist model was used to measure the static and dynamic technological innovation efficiency of research-oriented universities in the Yangtze River Delta from 2012 to 2018, and the panel Tobit model was used to analyze the influencing factors of the technological innovation efficiency of universities. The study shows that the overall technological innovation efficiency of research-oriented universities in the Yangtze River Delta is not high, but the overall total factor productivity is on the rise, and the annual average of Malmquist index is 1.033,which is greater than 1.Government support, human investment and achievement award are positively but not significant correlated with the technological innovation efficiency in colleges. Scientific and technological projects are significantly positively correlated with the technological innovation efficiency of research-oriented universities. Therefore, policy suggestions to improve the efficiency of scientific and technological innovation are given from the aspects of building a high-level scientific and technological innovation team, improving the cultivation mechanism of top-notch talents, paying attention to the spiritual incentive effect of achievement award, and optimizing the innovation investment structure.