Objective To investigate the effects of regular ball squeeze exercise on axillary venous flow velocity and complications in patients with a PICC line. Methods A total of 110 patients after PICC placement were randomized into two groups of 55 cases each. The control group was asked to complete a daily total of 500 ball squeezes , which could be splitted to perform in the morning, at noon, and in the evening. The intervention group was asked to do the same hand ball exercise after 3 meals, at 25-30 squeeze cycles (a cycle=squeeze for 10 s, and relax for 10 s) each time. Results The maximum velocity (Vmax) and the time average velocity (TAV) of the axillary vein were higher in the intervention group than in the control group at 21 and 28 days after PICC placement (P<0.01 for both). The incidence rate of venous thrombosis of upper extremity and catheter-related complications 28 days into placement in the intervention group was lower than in the control group, though the former indicator had statistical difference (P<0.05) and the latter without between the 2 groups (P>0.05). Conclusion Regular ball squeeze exercise can effectively improve axillary venous blood flow and reduce the incidence rate of venous thrombosis of upper extremity.