Objective: To investigate the expressions of the E3-ubiquitin ligase subunit Ring1B, lysine-specific histone demethylase 1 (LSD1) and cell cycle regulatory molecule P16 in pancreatic cancer and their relations with the prognosis of the patients. Methods: The distributions and expressions of Ring1B LSD1 and P16 proteins in the surgical specimens (cancer tissues and cancer-adjacent tissues) from 85 pancreatic cancer patients were determined by immunohistochemical staining, from which, 6 paired specimens were picked up for measurement of mRNA and protein expressions of Ring1B, LSD1 and P16 through qRT-PCR and Western blot, respectively. The correlations among their expressions in pancreatic cancer tissue, and relations of their expressions with the survival of the patients were analyzed. Results: The results of immunohistochemical staining showed that Ring1B and LSD1 were mainly expressed in the cytoplasm, while P16 protein was mainly found in the nucleus; the Ring1B and LSD1 expressions were significantly higher, while the P16 expression was significantly lower in pancreatic cancer tissue than those in cancer-adjacent tissue (all P<0.05); either the Ring1B or LSD1 expression had a negative correlation with P16 expression in pancreatic cancer (r=–476; r=–0.673, both P<0.05). The results of qRT-PCR showed that the average relative mRNA expression levels of Ring1B and LSD1 were significantly higher (8.908 vs. 1.947; 7.126 vs. 1.940, both P<0.05) and the average relative mRNA expression level of P16 in pancreatic cancer tissue was significantly lower (1.269 vs. 5.237, P<0.05) than those in cancer-adjacent tissue; the protein expression patterns of them were similar to their mRNA expressions as evidenced by Western blot analysis. The survival analysis showed that the survival rate in patients with high Ring1B or LSD1 expression was significantly lower than that in patients with low Ring1B or LSD1 expression (χ2=8.958, P=0.012; χ2=8.856, P=0.010), which in patients with high P16 expression was significantly higher than that in patients with low P16 expression (χ2=7.867, P=0.024). Conclusion: Ring1B and LSD1 expressions are increased and P16 expression is decreased in pancreatic cancer tissue. Ring1B and LSD1 may probably regulate P16 expression respectively through histone ubiquitination and demethylation, and thereby influence the prognosis of pancreatic cancer.