To evaluate the prognostic value of pre-therapeutic inflammatory markers before transarterial chemoembolization with degradable starch microspheres (DSM-TACE) in the treatment of hepatocellular carcinoma (HCC). A total of 155 patients (81% male, median age: 68 years) who underwent first-time DSM-TACE between 07/13 and 06/22 were included in the study. Inflammatory indices were dichotomized using median values. Cox proportional hazard model for univariate (UVA) and multivariate (MVA) analyses (hazard ratio; 95% CI, -value) and Kaplan-Meier analyses (overall survival (OS) in months; 95% CI; log-rank test) were performed. The median OS of the study cohort was 15.9 (12.9-20) months with a median survival according to BCLC stages A (12%), B (41%), and C (47%) of median not reached, 19.3 (15.3-27), and 7.2 (4.5-9.0) months, respectively ( < 0.0001). In the UVA, several inflammatory markers on OS were statistically significant with the systemic inflammatory response index (SIRI; ≤median (2.04) HR: 0.41 (0.19-0.89); = 0.024) and the lymphocyte to monocyte ratio (LMR; >median (1.82) HR: 0.44 (0.2-0.9); = 0.025) remaining statistically significant in MVA together with the BCLC stage ( = 0.0001), ALBI grade ( = 0.016), hepatic tumor burden (≤25% vs. >25%; = 0.006), and largest HCC lesion (≤5.5 cm vs. >5.5 cm; = 0.008). In subgroup analysis, patients with elevated LMR and reduced SIRI exhibited significantly prolonged overall survival (OS) in both BCLC B ( < 0.0001) and Child-Pugh A ( = 0.021) subgroups. The findings suggest that SIRI and LMR may serve as valuable tools in identifying BCLC B and Child-Pugh A patients who could potentially benefit better from DSM-TACE treatment. Nevertheless, further research is recommended to confirm these findings and to provide more comprehensive insights.