Objective To investigate the influencing factors for the prognosis of adult patients with chronic drug-induced liver injury (DILI). Methods A total of 255 patients who were diagnosed with chronic DILI by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to December 2018 were enrolled, and according to the liver function after 2 years, they were divided into non-recovery group and recovery group. The two groups were analyzed in terms of the clinical data including age, sex, body mass index, types of drugs used, type of DILI injury, severity of DILI injury, underlying diseases, laboratory markers, liver histology, and 2-year prognosis. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for the prognosis of chronic DILI. Results After 2 years of follow-up, 195 patients (76.5%) achieved the recovery of liver function, while 60 patients (23.5%) did not achieve such recovery. There were significant differences between the two groups in the type of DILI injury ( P =0.028), the proportion of patients with diabetes ( P =0.048), and the degree of liver fibrosis ( P < 0.001), and compared with the recovery group, the non-recovery group had significantly higher levels of baseline white blood cell count, platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, and total bile acid and a significantly lower level of cholinesterase (ChE) (all P < 0.05). The baseline characteristics were included in the univariate logistic regression analysis, and the results showed that PLT, ALT, AST, ChE, and fibrosis degree were significantly associated with the prognosis of chronic DILI (all P < 0.05). The multivariate logistic regression analysis of the above variables showed that PLT < 100×10 9 /L (odds ratio [ OR ]=3.592, 95% confidence interval [ CI ]: 1.128-11.438, P =0.003) and ALT > 2×upper limit of normal (ULN) ( OR =3.080, 95% CI : 1.331-7.127, P =0.009) were independent risk factors for the prognosis of chronic DILI. Conclusion When patients meet the diagnostic criteria for chronic DILI, the independent risk factors PLT < 100×10 9 /L and ALT > 2×ULN may be used to screen out the patients who are more likely to have poor prognosis.