Objective To investigate the clinical features of drug-induced liver injury (DILI) due to Tripterygium wilfordii preparation and concomitant medications in patients with rheumatoid arthritis (RA). Methods A retrospective analysis was performed for the clinical data of 112 RA patients with DILI caused by Tripterygium wilfordii preparations and concomitant medications who were treated in Honghu Hospital of Traditional Chinese Medicine from January 2014 to December 2019, and demographic data and the clinical features of DILI were observed to explore the influence of concomitant medications and underlying diseases on DILI. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups and further comparison between two groups. Results All 112 patients had a mean age of 48.13±14.38 years, and there were 81 female patients (72.32%). The most common underlying disease was nonalcoholic fatty liver disease (NAFLD) in 8 patients (7.14%), and as for concomitant medications, 70 patients (62.50%) were treated with Tripterygium wilfordii preparation combined with non-steroid anti-inflammatory drug (NSAID) or disease-modifying anti-rheumatic drug (DMARD). The main clinical manifestation was joint pain in 110 patients (98.21%). Among the 112 patients, 102 (91.07%) had abnormal results of liver biochemical examinations; 66 patients (58.93%) had an RUCAM score of 6-8 points, and 110 patients (98.21%) had mild (grade 1) liver injury. After liver-protecting treatment (for less than 6 months in all patients), all patients had an improvement in liver function without aggravation or death. The Tripterygium wilfordii preparation+glucocorticoid+NSAID/DMARD group with 22 patients had significant increases in the serum levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) compared with the Tripterygium wilfordii preparation+NSAID/DMARD group with 70 patients ( P < 0.05). The 8 patients with NAFLD had a significantly greater increase in serum alanine aminotransferase compared with the 90 patients without underlying diseases ( P < 0.05). Conclusion RA patients may develop DILI due to Tripterygium wilfordii preparation and concomitant medications, which is commonly observed in middle-aged women. Joint pain is the main clinical manifestation, and patients tend to have mild liver injury and good prognosis without marked chronicity. More severe liver injury is observed in patients with combined medication of glucocorticoids and NSAID/DMARD or those with the underlying disease of NAFLD.