To prospectively assess the feasibility, safety and efficacy of performing DEE-TACE using the Surefire Infusion System. This was an IRB-approved prospective study registered in clinicaltrials.gov (NCT03211598). A total of 15 patients with BCLC stage A or B HCC were enrolled. All patients underwent a standard angiogram and embolization using SIS (TriSalus, Westminster, CO). Embolization was performed using 1 vial of 100 micron Oncozene (Boston Scientific, Marlborough, MA) loaded with 50 mg of Doxorubicin and 100 or 250 micron Embozene (Boston Scientific, Marlborough, MA), as required. Treatment end-point was defined as reflux of contrast with catheter tip expanded or development of intrahepatic collaterals. All embolization procedures were performed by one of 3 fellowship trained interventional radiologist (AYK, GEL, EC). Initial follow-up imaging was obtained 8 weeks post treatment and every 8 weeks for the first 6 months then at 52 weeks post treatment. Disease response was evaluated based on the mRECIST criteria by 1 of 2 fellowship trained abdominal imager (DD or PK). Patients with recurrent or residual disease at any follow-up were treated in an “on-demand” fashion. Adverse events were assessed at 2 and 8 weeks post treatment and graded per CTCAE v 4.03. Pathologic assessment was performed by a pathologist specializing in HCC (BK). 15 patients with a total of 23 lesions underwent 20 separate treatments. During the study follow-up, 1 patient died, 2 enrolled in other trials, 1 treated with ablation, and 8 underwent transplantation. 2 patients were alive at 12 months and 1 is currently undergoing follow-up. There were no procedural complications or grade 3 or higher toxicities. The rates of CR, PR and SD at 8 weeks was 6/15 (40%), 7/15 (47%) and 2/15 (13%), respectively. The rates of CR, PR and PD at 6 month follow-up was 6/11 (55%), 4/11 (36%) and 1/11 (9%). Complete pathologic response was seen in 5/8 (63%) patients. The other 3 patients had >80% necrosis of their tumors. The SIS is safe for delivery of DEE-TACE with promising efficacy. A comparative study is needed to assess its potential benefit over standard catheters.