Objective Based on silencing information regulatory factor 1 (SIRT1)/high mobility group protein B1 (HMGB1)/nuclear transcription factor-κB (NF-κB) to investigate the inhibitory effect and mechanism of Qingerkang tea on hepatocyte inflammatory apoptosis in mice with carbon tetrachloride (CCl4) induced acute liver injury. Methods C57BL/6 mice were randomly divided into normal group, model group, SIRT1 agonist (resveratrol) group, Qingerkang tea low-dose, medium-dose and high-dose groups, and positive drug (dicycloalcohol tablets) group. The mice were given continuous intragastric administration for 14 days. Acute liver injury model was established by intraperitoneal injection of 0.5% CCl4 olive oil solution (5 mL/kg). The levels of alanine transferase (ALT), aspartate transferase (AST), lactate dehydrogenase (LDH) in serum and hydroxyproline (Hyp), malondialdehyde (MDA) and superoxide dismutase (SOD) in liver were determined by biochemical method. Serum levels of inflammatory tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (Elisa). Eosin-hematoxylin (HE) staining and TUNEL staining were used to detect the pathological morphology and apoptosis of liver tissues. The protein expressions of SIRT1, HMGB1 and NF-κB were detected by Western blotting. Results Compared with the normal group, the serum ALT, AST, LDH levels and liver tissue Hyp activity in the model group were significantly increased, the activities of MDA and SOD in liver tissue were significantly decreased, the levels of inflammatory factors TNF-α, IL-6 and IL-1β in the liver tissue were significantly increased, and there were obvious pathological injury and hepatocyte apoptosis in the liver tissue. The expression of SIRT1 protein in liver tissue decreased significantly, while the expression of HMGB1 and NF-κB protein increased. Compared with model group, the serum levels of ALT, AST, LDH and Hyp activity of liver tissue were significantly decreased, the activities of MDA and SOD in liver tissue were significantly increased, the levels of serum inflammatory factors TNF-α, IL-6 and IL-1β were decreased, the pathological injury of liver tissue and the apoptosis of liver cells were significantly improved. The expression of SIRT1 protein in liver tissue was increased, while the expression of HMGB1 and NF-κB protein were decreased in Qingerkang tea high-dose group and resveratrol group. Conclusion Qingerkang tea could effectively protect acute liver injury, and its mechanism may be related to regulating SIRT1/ HMGB1/ NF-κB signaling pathway and alleviating hepatocyte inflammatory apoptosis.