Objective:To evaluate the clinical application of water-filling with "four-eyes" sign under the guidance of ultrasound in nasal-jejunum intubation for critical patients.Methods:This study was a randomized controlled trial. Eighty patients who needed indwelling nasobenteric tube were selected from June 2021 to April 2022 in the Department of Critical Care Medicine, Xiangya Hospital, Central South University. They were divided into control group ( n=40) and experimental group ( n=40) by systemic randomization. For the patients in the experimental group, the intubation was performed by water-filling with "four-eyes" sign under the guidance of ultrasound. For the control group, the traditional method was applicated under the guidance of ultrasound. Using abdominal X-ray as the gold standard of successful pylorus posterior catheterization, the result of catheterization, time of operation, efficiency of positioning in the two groups were analyzed and compared. Results:In the experimental group, 38 cases were successfully intubated, 2 were failed; in the control group, 27 cases were successfully intubated, 13 were failed, and all the failed cases in the control group were then successfully intubated again by using method of the experimental group. The success rate of tube placement in the experimental group was 95.0% (38/40), which was higher than 67.5% (27/40) in the control group ( χ2 = 9.93, P<0.05). The average time of operation in the experimental group was (45.2 ± 14.2) min, which was significantly lower than (70.2 ± 17.7) min in the control group, the difference was significantly different ( t=-5.51, P<0.05). The specificity, sensitivity, positive predictive value, negative predictive value and diagnostic rate of nasal-jejunum intubation positioning in the experimental group were 100.0% respectively, higher than 38.4%, 77.7%, 72.4%, 45.4%, 65.0% in the control group; the false positive rate, false negative rate in the experimental group were both 0, lower than 22.2%, 61.5% in the control group, with statistically significant differences( χ2 values were 4.69- 16.97, all P<0.05). Conclusions:Water-filling with "four-eyes" sign under the guidance of ultrasound in nasal-jejunum intubation was a new method which can shorten the operation time and increase the success rate for intubation. It has relatively high positioning accuracy and possess valuable clinical application.