Objective To explore the application effect of precise prevention and control measures on reducing central venous catheter-related bloodstream infection (CRBSI). Methods Patients with central venous catheterization ≥48 hours in a tertiary first-class hospital from January 2019 to December 2020 were selected. January to December 2019 was pre-intervention period, the whole hospital began to implement precise prevention and control measures at the end of December 2019, and January to December 2020 was post-intervention period. Implementation rate of CRBSI prevention and control measures of health care workers and incidence of CRBSI among patients before and after intervention was compared. Results The implementation rate of CRBSI prevention and control measures in 2020 was 99.06%(191 504/193 324), which was higher than 87.90%(382 550/435 194)in 2019, difference was significant (χ²=21 046.64, P < 0.001). There were 54 and 11 cases of CRBSI in 2019 and 2020 respectively, there were no significant differences in gender, age, leukocyte count, procalcitonin and C-reactive protein between two groups of patients (all P>0.05). The total catheterization days in 2019 was 350 473 days, incidence of CRBSI was 0.15‰; the total catheterization days in 2020 was 186 856 days, incidence of CRBSI was 0.06‰, difference in incidence of CRBSI between two groups of patients was significant(χ²=5.912, P=0.015). Conclusion Implementation of precise prevention and control measures can reduce the incidence of central venous CRBSI in patients undergoing central venous catheterization.