Hemorrhage remains a leading cause of death after trauma, and developing a hemostat with excellent performance and good biosecurity is an extremely active area of research and commercial product development. Although oxidized regenerated cellulose (ORC) has been developed to address these problems, it is not always efficient and its biosecurity is not perfect. We aimed to refine ORC via a simple and mild neutralization method. The prepared neutralized oxidized regenerated cellulose (NORC) showed a superior gel property due to its chemical structure. The biological performance of both ORC and NORC was systematically evaluated; the results showed that ORC would induce erythema and edema in the irritation test, whereas NORC did not cause any adverse inflammation, indicating NORC had desirable biocompatibility. We further demonstrated that NORC confirmed to the toxicity requirements of International Organization for Standardization (ISO) standards; however, ORC showed an unacceptable cytotoxicity. The rabbit hepatic defect model stated that NORC exhibited better ability of hemostasis, which was attributed to its significant gel performance in physiological environment.