Gastric cancer is one of the most common malignant tumors in the digestive system, which often occurs in middle-aged and elderly people. Traditional Chinese medicine recognizes gastric cancer as a kind of tumor characterized by fluid deficiency, heat accumulation and the growing binding of toxins in the stomach. It is commonly treated with heat-clearing and detoxifying drugs in clinical practice. Hedyotis diffusa-Scutellaria barbata herb pair (HS) has the effects of clearing heat and detoxifying, promoting blood circulation, resolving carbuncle and expulsing boil, anti-inflammatory and analgesic, which are consistent with the etiology and pathogenesis of gastric cancer, therefore, it can be used for the treatment of gastric cancer. Modern pharmacological researches have confirmed that HS can play an anti-gastric cancer role by inducing cell apoptosis, inhibiting cell proliferation, inhibiting angiogenesis, improving immune microenvironment and down-regulating telomerase activity. Herein, this review summarizes the active ingredients and related mechanism responsible for the anti-gastric cancer effect of HS, which will provide the theoretical basis for its clinical use and the development of new drugs against gastric cancers.