Objective Use of 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 Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea on hepatocyte inflammatory apoptosis in mice with carbon tetrachloride (CCl₄ )-induced acute liver injury. Methods C57BL/6 mice were randomly divided into a control group; model group; resveratrol group; Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea low-, medium-, and high-dose groups; and a positive drug group. The mice were given continuous intragastric administration of the treatments for 14 days. An 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 the liver were determined by biochemical method. Serum levels of inflammatory tumor necrosis factor-α(TNF-α), interleukin (IL)-6, and IL-1β were determined by enzyme-linked immunosorbent assay. Eosin-hematoxylin and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining were used to examine the pathological morphology and apoptosis in liver tissues. The protein expression of SIRT1, HMGB1, and NF-κB were detected by Western Blot. Results Compared with those of the control group, the model group’s serum ALT, AST, and LDH levels and liver tissue Hyp activity were significantly increased; MDA and SOD activities in liver tissue were significantly decreased; the levels of inflammatory factors TNF-α, IL-6, and IL-1β in liver tissue were significantly increased; and there were obvious signs of pathological injury and hepatocyte apoptosis in the liver tissue. The expression of SIRT1 protein decreased significantly, while the expression of HMGB1 and NF-κB proteins increased, in liver tissue. Compared with those of the model group, the Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea high group and resveratrol group serum levels of ALT, AST, and LDH and liver tissue Hyp activity were significantly decreased; MDA and SOD activities in liver tissue were significantly increased; the levels of serum inflammatory factors TNF-α, IL-6, and IL-1β were decreased; and pathological injury to 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 the Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea high-dose group and resveratrol group(P<0.05 or P<0.01). Conclusions Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea effectively protects against acute liver injury, and its mechanisms may be related to the regulation of the SIRT1/HMGB1/NF-κB signaling pathway and the alleviation hepatocyte inflammatory apoptosis.