Simple SummaryThis retrospective study using the prospectively collected registry data of newly diagnosed, previously untreated hepatocellular carcinoma (HCC) evaluates the significance of systemic inflammatory markers (SIMs) to intrahepatic recurrence (IHR) after curative treatment. Out of 4076 patients who met the inclusion criteria, 52.6% experienced IHR. SIMs, including pre-treatment platelet-to-lymphocyte ratio (PLR), post-treatment changes of neutrophil-to-lymphocyte ratio PLR, and lymphocyte-to-monocyte ratio were significantly associated with the prognosis of early-stage HCC patients who received initial curative treatment. The prognostic significances of SIMs were consistent for IHR-free survival, early and late IHR, and overall survival.Systemic inflammatory markers (SIMs) are known to be associated with carcinogenesis and prognosis of hepatocellular carcinoma (HCC). We evaluated the significance of SIMs in intrahepatic recurrence (IHR) of early-stage HCC after curative treatment. This study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC between 2005 and 2017 at a single institution. Inclusion criteria were patients with Barcelona Clinic Liver Cancer stage 0 or A, who underwent curative treatment. Pre-treatment and post-treatment values of platelet, neutrophil, lymphocyte, monocyte, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) were analyzed with previously well-known risk factors of HCC to identify factors associated with IHR-free survival (IHRFS), early IHR, and late IHR. Of 4076 patients, 2142 patients (52.6%) experienced IHR, with early IHR in 1018 patients (25.0%) and late IHR in 1124 patients (27.6%). Pre-treatment platelet count and PLR and post-treatment worsening of NLR, PLR, and LMR were independently associated with IHRFS. Pre-treatment platelet count and post-treatment worsening of NLR, PLR, and LMR were significantly related to both early and late IHR. Pre-treatment values and post-treatment changes in SIMs were significant factors of IHR in early-stage HCC, independent of previously well-known risk factors of HCC.