Objective: To explore the application value of whole genome sequencing technology in severe sepsis, and to evaluate the effect of cluster nursing intervention. Methods: One hundred patients with severe sepsis admitted in Second Affiliated Hospital, Hunan University of Traditional Chinese Medicine from January 2017 to September 2018 were randomly divided into an intervention group (n=50) and a control group (n=50). White blood cell count (WBC), procalcitonin (PCT), C-reactive protein (CRP) and blood lactic acid (LAC) were compared between the two groups. The sequential organ failure assessment (SOFA) scores and acute physiology and chronic health evaluation II (APACHE II) scores of the two groups were compared. The hospitalization time of ICU was compared between the two groups. Results: On the first day of ICU, there was no significant difference in WBC, PCT, CRP and LAC between the two groups (P>0.05). The WBC, PCT, CRP and LAC of the intervention group were better than those of the control group on the 3rd and 7th day after admission to ICU (all P<0.05). On the first day of ICU, there was no significant difference in the APACHE II score and SOFA score between the two groups (P>0.05). On the 3rd day of ICU, APACHE II score and SOFA score of the intervention group were better than those of the control group (P<0.05), the difference was statistically significant. The hospitalization time of ICU in intervention group (9.2±1.6) d was significantly shorter than that in control group (14.3±1.8) d, the difference was statistically significant (P<0.05). Conclusion: The whole genome sequencing technology can accurately diagnose severe sepsis. The cluster nursing intervention can effectively improve the efficacy of sepsis, promote disease rehabilitation.