Objective To explore the effect of intensive nutritional support on patients with liver failure receiving plasma diafiltration treatment. Methods A total of 120 patients with liver failure undergoing plasma diafiltration treatment were enrolled and grouped according the time periods. From March to October 2022, 60 patients were included into the control group and were given routine nutritional intervention. From November 2022 to June 2023, 60 patients were included into the intervention group and given comprehensive intensive nutritional intervention such as night snacks on the basis of the control group. Then the nutritional improvement of the two groupswere evaluated. Results Fifty-six cases in the intervention group and 58 cases in the control group completed the study. After intervention, the levels of albumin and prealbumin, the Royal Free Hospital-Nutrition Prioritizing Tool score, NSR-2002 score in the intervention group were significantly better than those in the control group (all P<0.05), and the Child-Pugh score was significantly lower than the control group (P<0.05). The nutrition indicators of the two groups, including arm muscle circumference, triceps skinfold thickness, and BMI, were improved from pre-intervention level. Conclusion Intensive nutritional intervention can improve the nutritional status of patients with liver failure undergoing plasma diafiltration treatment, and enhance quality of life of the patients.