Objective To explore the clinical value of blunt separation method in reducing complications related to ultrasound-guided modified Seldinger technique (MST) peripherally inserted central catheter (PICC). Methods A total of 230 patients receiving PICC were randomly divided into observation group and control group (115 cases in each group) according to the random code generated by the random number table. The observation group was treated with blunt separation, while the control group was treated with scalpel. The success rates of one-time puncture, one-time catheterization and catheterization, the degree of intraoperative pain, and the incidence of errhysis and drug leakage at puncture site were compared between the 2 groups. Results There were no significant differences in gender, age, primary tumor source, or puncture blood vessel between the observation and control groups (all P>0.05). All patients were successfully catheterized. The success rate of one-time puncture was 95.7% (110/115) in the observation group and 94.8% (109/115) in the control group, with no significant difference (P=0.757). The successful rate of one-time catheterization was higher in the observation group (100.0%, 115/115) than in the control group (93.0%, 107/115), showing significant difference (P=0.007). The degree of pain during puncture and the incidence of errhysis were lower in the observation group than in the control group (both P<0.01). No exudation occurred in the observation group after catheterization, and a little exudation occurred in 4 cases (3.5%) of the control group (P=0.122). Conclusion The blunt separation method can improve the successful rate of one-time catheterization, relieve pain and reduce the incidence of errhysis at puncture site, making it worthy of clinical application.