Aims: Nonalcoholic fatty liver disease (NAFLD) may be crucial in subjects with familial hypercholesterolemia (FH). We aimed to evaluate the effect of the inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9-i) on steatosis biomarkers such as triglyceride-glucose index (TyG) and hepatic steatosis index (HSI) and analyse the role of TG/ HDL in this population before and after adding-on PCSK9-i. Methods: In this observational study, we evaluated 26 genetically confirmed FH patients with NAFLD and an LDL-C off-target despite high-intensity statins plus ezetimibe. All patients added PCSK9-i treatment and obtained biochemical analysis and TyG and HSI evaluation at baseline and after six months of PCSK9-i. Results: No difference of steatosis biomarkers was found after adding-on PCSK9-i therapy. In a secondary analysis, we divided the study population in two groups according to TG/HDL median value: high TG/HDL group (H-TG/HDL) and low TG/HDL group (L-TG/HDL). TyG and HSI were significantly lower in the L-TG/HDL than H-TG/HDL group (for TyG 9.05±0.34 vs 9.51±0.32; for HSI 38.43±1.35 vs 41.35±1.83, p value for both <0.05). After six months of PCSK9-i therapy, TyG and HSI were significantly reduced in the L-TG/HDL group after PCSK9-i therapy (7.5% and 8.4% respectively, p value for both <0.05) and these biomarkers were lower compared to H-TG/HDL group (for TyG 8.37±0.14 vs 9.19±0.12; for HSI 35.19±1.32 vs 39.48±1.33, p value for both <0.05). Conclusion: In conclusion, PCSK9-i therapy significantly ameliorate steatosis biomarkers in FH patients with low TG/HDL; our results appear to be consistent with a beneficial role of PCSK9- i on steatosis biomarkers in FH subjects with NAFLD.