Current knowledge on the etiology of hepatoblastoma remains limited. FTO gene has been documented as a susceptibility gene for several types of cancer. However, its role has not been characterized in hepatoblastoma. Herein, we intended to explore whether FTO gene single nucleotide polymorphisms (SNPs) contribute to the risk of hepatoblastoma. A multi-center case-control study was conducted including 358 cases and 1512 controls recruited from the night hospitals in China. Odds ratios (ORs) and 95% confidence intervals (CIs), for the association of FTO gene SNPs with hepatoblastoma risk, were estimated using conditional logistic regression models, adjusted for relevant confounding variables. Four SNPs (rs1477196 G > A, rs9939609 T > A, rs7206790 C > G, and rs8047395 A > G) in the FTO gene were genotyped. We detected a significant association between rs9939609 T > A and decreased risk of hepatoblastoma (TA vs. TT: adjust OR = 0.73, 95% CI = 0.54-0.99, P = 0.041; TA/AA vs. TT: adjust OR = 0.73, 95% CI = 0.55-0.97, P = 0.032). Compared to 0-3 protective genotypes, carriers with four protective genotypes showed enough strength to protect from hepatoblastoma (adjust OR = 0.65, 95% CI = 0.47-0.91, P = 0.012). In stratification analysis, we also detected a significantly decreased risk of hepatoblastoma in subjects with rs9939609 TA/AA or with four protective genotypes in some subgroups. Our results provided some clues for an association of FTO gene SNPs with hepatoblastoma risk in Chinese children.