We designed this study to explore how factors, especially knowledge, influence the use and prescriptions of antibiotics among physicians in China's county hospitals.A questionnaire was designed to evaluate the knowledge levels of physicians. The rates of antibiotic prescriptions were collected through on-the-spot investigations. The percentage of encounters with antibiotics prescribed and the percentage of encounters with antibiotics combination prescribed were used to measure antibiotics use. Univariate analysis and the generalized linear model were applied to analyze the knowledge levels among physicians as well as their antibiotic prescriptions.A total of 334 physicians in 60 county hospitals filled out the questionnaires, and 385,529 prescriptions were collected. The mean score of the questionnaire was a pass (62.8). The physicians in the eastern region of China demonstrated higher levels of knowledge than other regions (P = .08). Physicians with a higher score prescribed less antibiotics (P < .01) and less antibiotics combination (P = .07).The knowledge gap of Chinese physicians is evident and those with a higher degree of knowledge always prescribe fewer antibiotics. Targeted training and courses to educate physicians about the risks of over-prescription of antibiotics should be conducted to improve the practice of antibiotic prescriptions.