Abstract: Objective To investigate the efficacy of PICC placement via the greater saphenous vein and explore best approach for clinical catheterization in patients with superior vena cava syndrome (SVCS). Methods A total of 12 tumor patients with SVCS who were unable to place PICC into the superior vena cava for chemotherapy via central venous catheter (CVC) in our hospital between January, 2015 and August, 2016 were enrolled into this study. On the basis of evolution and consultation with patients, family members and doctors, PICC placement via the greater saphenous vein was performed according to PICC catheterization standard operation procedure (including marker, measurement, disinfect, puncture, catheter placement and fixation with IV3000). The clinical data of all patients were summarized and analyzed. Results The catheterization via saphenous vein was performed in all 12 patients with an success rate of 100%. The extubation was carried out in 11 cases when all courses of chemotherapy were completed, and 1 case gave up chemotherapy due to intolerable side effects of chemotherapy. There was no complication in all patients during the catheter indwelling period. Conclusion PICC placement via the greater saphenous vein is a safe and effective method for patients with SVCS who were unable to place PICC into the superior vena cava for chemotherapy. With certain clinical advantages, it solves the problems in intravenous infusions in the upper extremities and is worthy of clinical application.