Objective Twist1 is a transcription factor that is highly expressed in many human cancers and its expression is related to chemotherapy resistance. In this study, we aimed to enrich for cells with a high-level expression of Twist1 from human glioma cell line U87 and investigate their sensitivity to the chemotherapeutic agent cisplatin. Methods Twist1hi-U87 subsets were sorted through flow cytometry using Twist1 specific SmartFlareTM RNA probe. Unsorted U87 cells were served as control. Different concentrations of cisplatin were administered to the cells. Cell viability was measured by CCK-8 assay and apoptosis was detected by flow cytometry. Results The percentage of Twist1hi-U87 subpopulations in unsorted parental cells was 57.9%~69.8%. CCK-8 assay showed that Twist1hi-U87 subsets were more resistant to cisplatin than U87 cells at 24h, 48h (P＜0.05). In addition, Twist1hi-U87 subsets had a lower rate of apoptosis than did the parental U87 cells (14.07% ± 0.96% vs 20.4% ± 1.29%) (P＜0.05). Conclusion Twist1 is involved in cisplain resistance by inhibiting cisplatin-induced apoptosis.