Hypoxia is one of the characteristics of human and animal tumors. To investigate the association between hypoxia and the immune evasion of cancer cells, the present study examined paraffin sections of pancreatic tissues from patients with pancreatic carcinoma, chronic pancreatitis and normal pancreatic tissue and established a series of PANC‑1 cell lines, which were cultured under various hypoxic and normoxic conditions. The results demonstrated that the expression of hypoxia‑inducible 1α (HIF‑1α) in pancreatic carcinoma was significantly higher compared with that in the chronic pancreatitis and normal pancreatic tissues, which revealed that a hypoxic microenvironment existed in pancreatic carcinoma. HIF‑1α was inversely correlated with major histocompatibility complex class I chain‑related (MIC) genes, which indicated that hypoxia was involved in tumor immune evasion. The cell experiments demonstrated that the mechanism involved shedding of the MIC from the membrane of the pancreatic carcinoma cells, which then formed soluble (s)MIC. The sMIC genes downregulated natural killer (NK) group 2, member D and the cytotoxic activity of NK cells. Depending on its activity, the nitric oxide‑cyclic guanosine monophosphate‑protein kinase G signaling pathway can either increase or inhibit immune evasion of pancreatic cancer cells.