Objective：To investigate the mechanism of aberrant Sonic Hedgehog（Shh）signaling which found in medulloblastom patients’ Suppressor of Fused（Sufu）mutations，and to reveal the relationship between Shh pathway and tumor growth or development. Methods：To create Sufu variants expression plasmids，the influence of Sufu mutants on the expression level of Sufu-/- cell endogenous Gli1 were detected by quantitative real-time PCR and Western blot. The combination of Sufu mutants and Gli were detected by CO-IP assay. MTT assay were used to evaluate the effects of Sufu variants on growth and proliferation of human medulloblastoma cells（DAOY）. Results：Quantitative PCR and Western blot experiments found that Sufu missense mutant（H87R）expression level of endogenous Gli1 showed wild type inhibition level，three nonsense mutants（R146X，R299X，W430X）of endogenous Gli1 expression level increased obviously；Under normal conditions，WT-Sufu can be combined with Gli1 protein，The CO-IP experiment found that the mutants of Sufu had different degrees of damage to the combination of Gli1 protein. The protein turnover rate experiment showed that Sufu mutants could be degraded by proteasome pathway and MTT assay showed that Sufu mutants lost their ability to inhibit the growth and proliferation of human medulloblastom DAOY cells. Conclusion：Clinically observed mutations in Sufu can drive tumor growth and further elucidates Sufu’s role in binding to and suppressing Gli function.