The peripheral nervous system significantly determines the fate of solid tumors and their microenvironment. In neurotropic malignancies such as pancreatic and prostate cancer, denervation in animal models demonstrate significantly delays in tumor initiation and progression, underscoring the critical neural dependency of these cancers. While tumor innervation establishes a structural basis for the neuromodulatory effects, the degree of innervation exhibits marked heterogeneity across tumor types, and its regulatory mechanisms remain poorly characterized. In this study, we screened genes associated with innervation status in pancreatic cancer and identified the splicing factor SRSF12 as a critical gene related to tumor innervation. In clinical samples, SRSF12 was expressed at low levels in pancreatic cancer tissues, and its downregulation was linked to poor prognosis in patients. Then we crossed Kras mutation and Srsf12 knockout mice (Kras