Background and Aims: In Europeans, variants in the hy-droxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver dis-ease (MAFLD). The impact of these variants in ethnic Chi-nese is unknown. The aim of this study was to investigate the potential associations in Chinese patients. Methods: In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic re-gression was used to test the association between the single nucleotide polymorphisms and liver histology. Results: In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR):2.93 (1.20–7.17), p=0.019 for the additive model; OR: 3.32 (1.39–7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from Eu-ropean cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24–0.98), p=0.043 for the additive model; OR: 0.62 (0.40–0.94), p=0.025 for the dom-inant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HS-D17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis. Conclusions: HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD popula-tion but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for study-ing diverse populations in genetic studies in order to fine map genome-wide association studies signals.