Aim To investigate the predictive value of levels of serum peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) mRNA and irisin in patients with acute ischemic stroke. Methods 161 patients with acute ischemic stroke were divided into non secondary hemorrhagic transformation (HT) group (97 cases) and secondary HT group (64 cases) according to the presence or absence of secondary HT. The levels of PGC-1α mRNA and irisin in serum were detected by real-time quantitative PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) respectively; Triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC) and creatinine were detected by automatic biochemical analyzer. The correlation between serum PGC-1α mRNA, irisin levels and blood lipids in patients with secondary HT to acute ischemic stroke was analyzed, the predictive value of serum PGC-1α mRNA and irisin levels was analyzed by receiver operating characteristic (ROC) curve, and the influencing risk factors were explored. Results The levels of PGC-1α mRNA, irisin and TG were lower in secondary HT group than those in non secondary HT group, while the level of HDLC in secondary HT group was higher than that in non secondary HT group (P＜0.05); The serum PGC-1α mRNA and irisin of acute ischemic stroke patients with secondary HT were positively correlated with TG level (P＜0.05), and negatively correlated with HDLC level (P＜0.05); The area under the curve (AUC) of serum PGC-1α mRNA and irisin levels in predicting secondary HT in patients with acute ischemic stroke was 0.865 and 0.893, the specificity was 85.9% and 87.5%, and the sensitivity was 74.2% and 82.5%, respectively; The AUC of the combined diagnosis was 0.960, the specificity was 89.1%, and the sensitivity was 87.6%; In addition, PGC-1α mRNA and irisin were protective factors of secondary HT in patients with acute ischemic stroke (P＜0.05), and HDLC was an independent risk factor (P＜0.05). Conclusion The levels of serum PGC-1α mRNA and irisin in patients with secondary HT are significantly lower than those without HT, which may be of great value in predicting the occurrence of HT.