Objective To compare the outcomes of PICC placed via the middle segment of the femoral vein and femoral central venous catheter (CVC) in children with hematological malignancies. Methods We retrospectively studied 140 children who were treated in our hospital from January 2014 to June 2019. Sixty-seven cases were placed with PICC via the middle segment of the femoral vein, and 73 cases had femoral CVC. The cost, catheter insertion time, catheter-indwelling-day,and complications were compared. Results The PICC group showed statistically less total cost and average daily maintenance cost, shorter catheter insertion time, and longer catheter-indwelling-day compared with the femoral CVC group (P＜0.01 for all). There were significant differences between the two groups in access site infection, catheter blockage and total complications (P＜0.05，P＜0.01), but no significant differences in catheter-related bloodstream infection, extubation, phlebitis, etc. (P＞0.05 for all). Conclusion PICC placed via the middle segment of the femoral vein is superior to femoral CVC in medical cost, catheterization time, indwelling time and catheter related complications.It can be a feasible and safe alternative route of central venous access for children with hematological malignances.