Objective To compare the effect of three tunneled PICC catheterization methods in malignant tumor patients. Methods A total of 644 malignant tumor patients with tunneled PICC catheterization were randomized into a conventional group (n=208),whose tunnel was established by using conventional method; an experimental group A (n=216), whose tunnel was established additionally by using 0.5% lidocaine to separate the subcutaneous tissue of tunnel site; and an experimental group B (n=220), whose tunnel was established by using normal saline to separate the subcutaneous tissue of tunnel site on the basis of the conventional method. Results There were significant differences among the three groups in total intraoperative bleeding weight, pain score during catheterization, incidence of bleeding at the puncture point 24 hours after catheterization, and once success rate of catheter extraction from the tunnel （all P＜0.05）.When the above indicators were compared further between any two groups of the three, there were significant differences between the conventional group and the experimental group A and B （P＜0.05,P＜0.0167）, while there were no significant differences between the experimental group A and the experimental group B （all P＞0.05）.In the conventional group, 3 patients （1.44%） suffered from nerve injury, and 5 patients （2.40%） experienced accidental artery injury.In the experimental group A, 2 patients （0.93%） encountered local anesthetic drug induced poisoning reaction. Conclusion In tunneled PICC catheterization, the establishment of tunnel by using normal saline to separate subcutaneous tissue can reduce bleeding, alleviate pain, improve the success rate of catheter extraction, and has higher safety.