Objective To investigate and compare the effects of succinylated gelatin injection and saline priming on the first hour blood pressure in critically ill patients receiving continuous renal replacement therapy (CRRT). Methods Inpatients who received continuous venous-venous dialysis filtration therapy in the intensive care unit of West China Hospital of Sichuan University between January and May 2024 were selected. The patients were randomly divided into an experimental group (colloidal solution group) and a control group (crystalloid solution group) in a 1∶1 ratio. The colloidal solution group used succinylated gelatin injection as the priming solution, and used the dual connection method to draw blood to the machine. The patient’s systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate at 10 minutes before and 0, 1, 3, 5, 10, 30 and 60 minute after CRRT initiation, the name and dosage of vascular compression drugs pumped intravenously at 0, 30 and 60 minutes, and the liquid inlet and outlet in the first hour were monitored and recorded. The crystalloid solution group used normal saline as the priming solution, and the rest of the methods were the same as those of the colloidal solution group. Two groups of patients were compared for changes in blood pressure and heart rate during the first hour of CRRT, as well as the incidence of hypotension. Results A total of 208 patients were included, with 104 cases in each group. There was no significant difference in baseline data between the two groups (P>0.05). At 3 minutes after CRRT, the systolic blood pressure of the crystalloid solution group was lower than that of the colloidal solution group [(122.56±23.82) vs. (129.43±25.46) mm Hg (1 mm Hg=0.133 kPa); t=−2.005, P=0.046]. There was no statistically significant difference in diastolic blood pressure, mean arterial pressure, or heart rate between the two groups at different time points (P>0.05). The intra group comparison results showed that the systolic blood pressure of the crystalloid solution group decreased compared to before at 1, 3, 5, and 10 minutes after CRRT (P<0.05), while the diastolic blood pressure and mean arterial pressure decreased compared to before at 3, 5, and 10 minutes after the start of CRRT (P<0.05); there was no statistically significant difference in blood pressure of the colloidal solution group among different time points after the start of CRRT (P>0.05). The heart rate of the crystalloid solution group was higher at 10 minutes after the start of CRRT than at 3 minutes after CRRT (P=0.045); 60 minutes after the start of CRRT, the heart rate in the colloidal solution group was lower than that 0 minutes after CRRT (P=0.032); there was no statistically significant difference between the two groups at other time points within each group (P>0.05). On the first hour of CRRT, there was a statistically significant difference in the incidence of hypotension between the two groups [33 cases (31.7%) vs. 18 cases (17.3%); χ2=5.845, P=0.016]. Conclusions The use of colloidal solution pre-flushing is more advantageous to improving the decrease in blood pressure in the first hour of CRRT in severe patients than crystalloid solution group pre-flushing. And it can reduce the incidence of hypotension in the first hour of CRRT in severe patients.