To investigate the effect of continuous blood purification on peripheral blood nucleotide-binding oligomerization receptor protein 3 (NLRP3) and intestinal barrier function in patients with sepsis. Methods A total of 83 patients with sepsis and non-sepsis admitted to the Intensive Care Center of the First Affiliated Hospital of Xinjiang Medical University from May 2019 to May 2021 were selected. On the basis of analgesia, sedation, fluid resuscitation and anti-infection treatment, the patients were divided into CBP group (n=24), conventional treatment group (n=35) and non-sepsis group (n=24) according to different treatment methods. The general data, underlying diseases, infection sites, inflammatory factors, creatinine, AGI score, APACHE Ⅱscore and 28-day prognosis of patients in each group after admission to ICU were collected and analyzed retrospectively. Results There were no significant differences in gender, underlying diseases, and infection sites among the three groups of patients, but the baseline APACHE Ⅱ score of patients in the sepsis CBP treatment group was significantly higher than that of the non-sepsis group and the conventional treatment group. Compared with before the machine, the sepsis CBP group had lactate and plasma/urea nitrogen (BUN) 3 days after the machine was used, peripheral blood lymphocyte NF-κB p65, NLRP3, Caspase-1, ASC; IL-1β in serum, IL-18, I-FABP, AGI score significantly decreased (all P＜0.05). The 28-day mortality in the CBP treatment group was 70.83%, which was significantly higher than in the conventional sepsis group (28.57%) and the non-sepsis group (16.67%). Conclusion Blood purification treatment may reduce the activation of NLRP3 inflammasomes in peripheral blood lymphocytes in sepsis patients, and then reduce the level of inflammatory factors in patients with sepsis, and improve the barrier function of the gastrointestinal tract of the patient; but the way through which blood purification improves the barrier function of the gastrointestinal tract still needs further research.