To explore the clinical application value of intracavitary electrocardiogram (ECG) localization combined with ultrasound in central venous catheterization in critically ill patients. A total of 103 patients who were treated in the intensive care unit of our hospital from October 2020 to June 2023 were selected as the study subjects, and according to the differences in their central venous catheter placement methods, they were divided into study group (n = 52, receiving ultrasound combined with intracavitary ECG localization for catheterization) and control group (n = 51, receiving routine catheterization). The differences in the catheter placement accuracy, catheter depth, catheter placement duration, incidence of catheter-related complications, length of stay, and hospitalization expenses between the 2 groups were compared. The analysis utilizing X-ray for catheter tip positioning indicated that the catheter tip placement rate was higher in the study group than in the control group, and the catheter tip malposition rate was lower than in the control group (P < .05). There was no statistical significance in the catheter depth between study group and control group (P > .05), and the catheter placement duration of study group was significantly lower than that of control group, with statistical significance (P < .05). One case of partial catheter blockage, one case of catheter-related bloodstream infection, and one case of phlebitis were observed in study group, with an overall incidence of complications of 5.77% (3/52), which was significantly lower than 21.57% (11/51) of control group (P < .05). The length of stay and hospitalization expenses in study group were significantly lower than those in control group, with statistical significance (P < .05). The combined use of ultrasound and intracavitary ECG localization in critically ill patients undergoing central venous catheterization can help increase the success rate of catheter placement, shorten the catheter placement duration, reduce the incidence of various catheter-related complications, and also reduce the length of stay and hospitalization expenses.