BACKGROUND Empathetic psychological care improves mood and enhances the quality of life in critically ill patients. AIM To study the impact of combining 222-nm ultraviolet (UV) disinfection with empathetic psychological care on emotional states, nosocomial infection rates, and quality of life in critically ill patients. METHODS A total of 202 critically ill patients admitted to Beijing Ditan Hospital (December 2023 to May 2024) were randomly assigned to control (Ctrl, n = 101) or observation groups (Obs, n = 101). The Ctrl group received 222-nm UV disinfection and routine care, while the Obs group received 222-nm UV disinfection with empathetic psychological care. Emotional states [Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS)], hospital infection rates, quality of life (36-Item Short Form Health Survey), and patient satisfaction were evaluated. RESULTS At baseline, there were no significant differences in SAS and SDS scores between the groups (P > 0.05). Following care, both groups demonstrated reductions in SAS and SDS scores, with the Obs group exhibiting a significantly greater reduction (P < 0.05). The Obs group also experienced a significantly lower overall hospital infection rate (P < 0.05). Similarly, while baseline 36-Item Short Form Health Survey scores did not differ significantly between the groups (P > 0.05), post-care scores improved in both groups, with a greater improvement observed in the Obs group (P < 0.05). Additionally, the Obs group reported higher patient satisfaction ratings (P < 0.05). CONCLUSION The combination of 222-nm UV disinfection and empathetic psychological care improves emotional states, reduces hospital infection rates, enhances the quality of life, and increases patient satisfaction among critically ill patients.