Oxidative stress is defined as the excessive production of reactive oxygen species (ROS) ( 4) and perturbation of the cell’s redox balance ( 5) in a manner that cannot be counteracted by antioxidants. To facilitate a breakthrough in the safety and efficacy of liver cancer treatment, there is an urgent need to develop new treatments to help increase patient life expectancy and the clinical benefits. Unfortunately, most patients are not eligible for these curative treatments when they are at the advanced stages of the disease. Although treatment strategies have improved significantly, they mainly involve surgery, chemotherapy, radiotherapy, and immunotherapy ( 3). Epidemiological data from the United States in 2018 shows that between 20, the mortality of patients suffering from liver cancer increased by 2.7% per year among women and 1.6% per year among men ( 2). Liver cancer is the sixth most common type of malignant tumor in the world and the second most common cause of tumor-related deaths ( 1). This effect manifests at least partially through immunomodulation mediated apoptosis. WNQP can inhibit the growth of HepG2- and SMMC-7721-xenografted tumors in nude mice and BALB/c mice. Further results confirmed that this regulation occurred via the regulatory effects of WNQP on Nrf2 signaling. In BALB/c mice, WNQP regulated immune function, inferred from the modulation of immune-related cytokines such as interleukins, interferon, tumor necrosis factors, and chemokines. WNQP inhibited tumor growth, but failed to affect bodyweight and organ structures (liver and spleen), confirming that it was safe to use in mice. The effects of WNQP against liver cancer were first systematically confirmed in HepG2- and SMMC-7721-xenografted nude mice and BALB/c mice models. The liver, spleen, and kidney were collected for histopathological examination. The tumors were removed, lysed, and subjected to proteome profiling, enzyme-linked immunosorbent assay, and western blotting. After the last dose, mice were sacrificed. The bodyweight of each mouse was monitored every day, and the tumor size was measured using vernier caliper before each round of WNQP administration. The mice were administered WNQP for 2 weeks. We established HepG2- and SMMC-7721-xenografted tumor models in nude mice and BALB/c mice. This study aimed to investigate the role of WNQP in inhibiting tumor growth in hepatocellular carcinoma model mice and determine its mechanism of action. However, the mechanism of its pharmacological action against liver cancer is not clear. The Wan-Nian-Qing prescription (WNQP), an herbal composite containing Ornithogalum caudatum, has been used in China for several years for cancer treatment. 3R&D Department, Jilin Tianlitai Pharmaceutical Co.2School of Life Sciences, Jilin University, Changchun, China.1Department of Pharmacy, Changchun University of Chinese Medicine, Changchun, China.Xinrui Zhang 1,2†, Xin Liu 2†, Yue Zhang 1,2, Anhui Yang 2, Yongfeng Zhang 2, Zhijun Tong 3, Yingwu Wang 2* and Ye Qiu 1*