Objective To analyze the effect of cluster-based nursing on catheter-related infection rate in ICU severe patients. Methods A total of 68 ICU severe patients in our hospital were taken as the clinical objects, and they were randomly divided into routine intervention group (34 cases) and cluster-based intervention group (34 cases). The catheterrelated infection rates, intubation time, ICU hospital stay and nursing effects in the two groups were compared. Results The catheter-related infection rate in the routine intervention group was 20.59% which was obviously higher than that in the cluster-based intervention group 2.94%, and their difference was statistically significant(P<0.05), the intubation time and hospital stay in the routine intervention group were obviously longer than those in the clusterbased intervention group, and their differences were statistically significant(P<0.05), the scores of nursing indicators in the cluster-based intervention group were higher than those in the routine intervention group, and their differences were statistically significant(P<0.05). Conclusion The cluster-based nursing which has significant nursing effect in ICU severe patients, can not only reduce the incidence of catheter-related infection, but also shorten the ICU hospital stay. Thus, it is worthy of clinical application.