In this study, we showed that SMO and GLI1 genes have a key role in tumor development, and our experimental results also showed that the GLI1 gene and its upstream SMO gene have a greater prognostic impact on mesothelioma patients, and we found that the survival time of mesothelioma patients was significantly longer when SMO and GLI1 genes were lowly expressed. This evidence concerns the gene SMO and mesothelioma.