Objective: To explore pathogens distribution, drug resistance and influencing factors of nosocomial infection in intensive care unit (ICU). Methods: A retrospective analysis was performed on pathogens and their drug resistance in the 80 patients with nosocomial infection in ICU of Shangrao People"s Hospital between January 2022 and December 2024, and the influencing factors of nosocomial infection were analyzed. Results: In the 80 patients, there were 126 strains of pathogens, including 92 strains (73.02%) of Gram-negative bacteria and 34 strains (26.98%) of Gram-positive bacteria. The drug resistance rate of Staphylococcus aureus to penicillin was as high as 93.33%, while drug resistance rate of Staphylococcus epidermidis to penicillin was 100.00%. The drug resistance of Klebsiella pneumoniae and Escherichia coli was high to ampicillin, and drug resistance rates of Pseudomonas aeruginosa to multiple antibiotics were >88.00%. Long stay in ICU, improper use of antibiotics and invasive operation were main factors of nosocomial infection in ICU and drug resistance. Conclusion: Gram-negative bacteria are main pathogens of nosocomial infection in ICU, while Gram-positive bacteria are common and have high drug resistance. Long hospital stay, antibiotics abuse and invasive operation are main reasons for infection and drug resistance. It is necessary to strengthen infection prevention and optimize the use of antibiotics.