Body Recent data have suggested the possibility of increased risk of HCC during and after DAAs treatment in HCV patients with advanced liver disease. We have therefore analyzed incidence of “de novo” HCC in a large cohort of HCV patients with advanced liver disease treated with oral DAAs and monitored by the NAVIGATORE web-based platform in Italy. 2279 HCV patients (66.6% males, 85.7% with cirrhosis, of whom 91% Child A and 9% Child B, 62% HCV-1, 11.2% HCV-2, 18.5% HCV-3, 8.45% HCV-4, ) were included. Patients with a past history of HCC were excluded. The 2279 patients were treated with approved DAAs regimens and monitored monthly. At the time of this analysis, mean follow-up from initiation of DAA therapy was 224.9 days. During this period, 27 patients developed HCC, and the overall calculated incidence x100 patient-years was 2.1 (95% CI : 1.40-3.10). The corresponding incidence values in different subgroups are described in the table. These values were not significantly different by log-Rank test . HCC was diagnosed at week 4 in 3 patients, at week 8 in 2 patients , at week 12 in 6 patients, between week 12 and week 24 in 7 patients and after end of treatment in 9 patients.HCC was nodular with a typical vascular pattern in 46% while in 54% HCC had a more aggressive pattern being infiltrative and multifocal. SVR12 was achieved in 20 out of 27 patients who developed HCC, while the remaining 7 patients were relapsers. Multivariate analysis indicated that only baseline AST and Platelets count were statistically associated with HCC risk, while gender, Age, HCV genotype and DAA regimen were not. The best baseline predictor of the HCC risk was APRI, and the HCC risk increased linearly by 10% at each 1 point increase in APRI value. These results indicate that in cirrhotic patients the incidence of HCC during the first 6-9 months following initiation of DAAs therapy is not different from that expected in untreated patients according to historical controls. However, the atypical HCC pattern seen in about half of the cases deserves better understanding. HCC incidence (x100patient-yrs) Males /Females 2.0 / 2.2 HCV1/HCV2/HCV3/HCV4 1.8 / 2.0 / 2.9 / 3.0 F3/Cirrhosis/Child A/Child B 0.7 / 2.2 / 1.9 / 4.1 SOF/RBV 3.7 SOF/LDV +/RBV 1.5 SOF/SMV +/RBV 1.2 SOF/DCV +/RBV 0.9 OBV/PTV/r + DSV +/RBV 2.3