Conclusions: Our results highlight the value of CREB3L1 as a predictive biomarker for the prognosis and immunotherapy efficacy in multiple cancers, and CREB3L1 seems to play key roles in the tumor immune microenvironment, suggesting the role of CREB3L1 as a promising biomarker for predicting the prognosis and immune-related signatures in diverse cancers. Here, CREB3L1 is linked to cancer.