<b><i>Introduction:</i></b> The impact of direct antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial. One important aspect of this controversy is the changing pattern of HCC. <b><i>Objective:</i></b> In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs. <b><i>Methods:</i></b> A total of 51 HCC patients after DAA treatment and 54 HCC patients without DAA treatment were included. The diagnosis of HCC was based on typical dynamic CT and/or MRI criteria in both groups. Liver status was assessed by means of the fibrosis 4 index (Fib-4), Child-Pugh classification, and model for end-stage liver disease (MELD). HCC infiltrative pattern, portal vein thrombosis (PVT), local and distant metastases, and α-fetoprotein (AFP) level were compared in the 2 groups. The staging of HCC and treatment decisions were made in both groups following the Milan criteria, Barcelona Clinic Liver Cancer staging, tumor-node-metastasis staging, and Cancer of the Liver Italian Program categorization. <b><i>Results:</i></b> The mean age of the HCC patients after DAA treatment (59.1± 7.4 years) was older than that of the HCC patients without DAA treatment. There was no significant difference between groups regarding sex distribution. The mean Fib-4 score (4.84 ± 3.53) was significantly lower in HCC patients after DAA treatment than in those without DAA treatment. The frequency of the infiltrative HCC pattern, PVT, and regional lymph node metastasis was significantly higher in HCC patients after DAA treatment than in those without DAA treatment (<i>p</i> ≤ 0.05); mean AFP level (5,085.2 ± 11,883.2 ng/mL) was also significantly higher. HCC patients after DAA treatment had significantly advanced stages and limited treatment options (<i>p</i> ≤ 0.05). <b><i>Conclusion:</i></b> The changing HCC pattern after DAA treatment may suggest the need for new HCC staging and treatment protocols.

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