Abstract: This study aims to screen cuproptosis-related genes and diagnostic biomarkers in non-alcoholic steatohepatitis（NASH） by using bioinformatics methods, and to predict the traditional Chinese medicine for the treatment of NASH by regulating cuproptosis-related genes. The GSE89632 data set was obtained from the GEO database as the training set, and differentially expressed cuproptosis-related genes（DECRGs） were extracted. The R4.2.2 software was used to analyze the correlation and enrichment of DECRGs. Based on DECRGs, NASH patients were classified, machine learning models were constructed to screen key genes, and the accuracy of machine learning model was verified. The traditional Chinese medicine that regulates cuproptosis-related genes therapy for NASH was predicted by COREMINE database. Traditional Chinese Medicine Inheritance Computer System v3.5 was used to mine the law of medication. Nine DECRGs were screened, and there were mutual regulation between DECRGs. Enrichment analysis showed that DECRGs mainly mediated lipoic acid metabolism, carbon metabolism and citrate cycle in the treatment of NASH. Consensus clusters divided NASH patients into three clusters. Support vector machine（SVM） model is the most accurate machine learning model. NFE2L2, LIAS, GLS, GCSH and PDHB were the five cuproptosis-related genes most associated with NASH, which can be used as diagnostic biomarkers of NASH. The four qi of traditional Chinese medicine regulating copper death gene therapy for NASH was mainly cold, warm and neutral, the five flavors were mainly bitter, sweet and pungent, and mainly belong to the liver and spleen channel. The main efficacy was deficiency supplementing, clearing heat, blood invigorating and stasis dissolving. This study suggests that cuproptosis-related genes, diagnostic biomarkers and the corresponding medication rules of traditional Chinese medicine in NASH are obtained, which provide a new idea for the clinical application and new drug research and development of traditional Chinese medicine in the treatment of NASH.