Pancreatic cancer has one of the worst prognoses in the world, which suggests that the tumor microenvironment, which is characterized by hypoxia and immunosuppression, plays a significant role in the prognosis and progression of pancreatic cancer. We identified PLAU, LDHA, and PKM as key genes involved in pancreatic cancer hypoxia through GO/KEGG enrichment related hypoxia pathways and cox regression, established prognostic models, and studied their relationship to immune invasion through bioinformatics using R and related online databases. We verified the high expression of PLAU, LDHA, and PKM in pancreatic cancer cells using qPCR in vitro, and we also discovered that the expression of PLAU, LDHA, and PKM in hypoxic pancreatic cancer cells differed from that in normal cultured pancreatic cancer cells. Finally, we discovered that our prognostic model accurately predicted postrain in pancreatic cancer patients with hypoxia and immune infiltration.