Objective: To investigate the relations of DNA topoisomerase II IIα (Topo IIα) and class III β tubulin (TUBB3) expressions in breast cancer tissue with the efficacy of anthracycline- and taxane-based neoadjuvant chemotherapy. Methods: Sixty-four women with primary breast cancer were enrolled, and they were randomly designated to receive anthracycline-based regimen (20 cases), taxane-based regimen (20 cases) or anthracycline plus taxane-based regimen (24 cases) respectively, and efficacy evaluation was conducted after 3-4 cycles. The expressions of Topo IIα and TUBB3 in the needle aspiration specimens from these patients before chemotherapy were detected by immunohistochemical staining. Results: The response rate for anthracycline-based, taxane-based and combination-based regimen was 50.00%, 35.00% and 70.83% respectively, but no statistical difference was found among the three regimens (P=0.128). Patients with positive Topo IIα expression had better response to anthracycline-based regimen than those with negative Topo IIα expression (P=0.023), while the response to taxane-based regimen was not associated with Topo IIα expression status of the patients (P=0.642); patients with positive TUBB3 expression showed poorer response to taxane-based regimen than those with negative TUBB3 expression, but the difference did not reach a statistical significance (P=0.057); patients with co-positive Topo IIα and TUBB3 expression were sensitive to anthracycline-based regimen, while those with positive Topo IIα expression and negative TUBB3 expression had better response to taxane-based regimen (P=0.015); the efficacy of combination-based regimen showed no relation with either Topo IIα or TUBB3 expression status (P>0.05). Conclusion: Breast cancer patients with positive Topo IIα expression may obtain better results with anthracycline-based chemotherapy, so it may be used as a predictor for making a personalized treatment plan. However, whether TUBB3 can be used as a predictor for tailored chemotherapy still needs further investigation with larger sample size.