Background: Previously, we showed that addition of lobaplatin (L) to taxane combined with anthracycline could improve the pathologic complete response (pCR) rate and lengthen survival significantly if employed as neoadjuvant therapy in patients with triple-negative breast cancer (TNBC). We evaluated the efficacy and safety of neoadjuvant chemotherapy of taxane (T) combined with lobaplatin (L) or anthracycline (E) for patients with TNBC. Methods: Ninety-five patients with TNBC (stage I–III) who had not undergone any type of treatment were divided randomly into two groups: TL (docetaxel at 75 mg/m² and lobaplatin at 30 mg/m², D1, one cycle = 21 days, a total of six cycles) or TE (docetaxel at 75 mg/m² and epirubicin at 80 mg/m², D1, one cycle = 21 days, a total of 6 weeks or epirubicin at 80 mg/m² and cyclophosphamide at 600 mg/m², sequential docetaxel at 75 mg/m², D1, one cycle = 21 days, a total of eight cycles). Efficacy was evaluated every two cycles. The final surgical procedure was completed after fulfillment of neoadjuvant chemotherapy. The primary endpoint was the total pathologic complete response (tpCR) rate. The secondary endpoints were the objective response rate (ORR), safety, event-free survival (EFS), and overall survival (OS). The exploratory endpoint was biomarker analysis. Results: From June 2019 to November 2022, 97 patients were screened. Finally, 95 patients were enrolled. The median age of the study cohort was 49 years. Nine patients (9.5%) had stage-I disease, 61 patients (64.2%) had stage II, and 25 patients (26.3%) had stage III. Sixty-five patients (68.4%) had Ki67 ≥40% and 30 patients (31.6%) had Ki67 < 40%. Seventy patients (73.7%) were cytokeratin (CK)5/6+ and 25 patients (26.3%) were CK5/6−. Of 95 patients, 47 were in the TL group and 48 in the TE group. The tpCR rate in the TL group was 46.8% (22/47), which was significantly higher than that in the TE group (22.9% (11/48); odds ratio (OR) = 2.960, 95% confidence interval (CI) = 1.223–7.164, P = 0.016). The ORR in the TL group was 95.7% (45/47), which was significantly higher than that in the TE group (75.0% (36/48); OR = 27.500, 95% CI = 1.576–35.683, P = 0.011). The prevalence of grade III/IV neutropenia in the TE group was 41.0% (9/22), which was significantly higher than that in the TL group (7.7% (2/26); OR = 8.308, 95% CI = 1.557–44.320, P = 0.013). There was no significant difference in the prevalence of other adverse reactions between the two groups. Conclusions: In the neoadjuvant treatment of TNBC, the TL regimen had a higher tpCR rate and ORR than those of the TE regimen, and was safer. Clinical trial information: ChiCTR1900023776.