Bronchoscopy has been widely used for the therapy of lung cancer. This study aimed to evaluate the therapeutic efficacy and adverse reactions of bronchoscopic intratumoral injection of endostar and cisplatin in patients with lung squamous cell carcinoma (LSCC). A total of 40 LSCC patients who underwent conventional chemoradiotherapy were included in this study, and 20 of them received a bronchoscopic injection of endostar and cisplatin as an additive therapeutic modality (treatment group). The clinical response rate, progression-free survival (PFS), and adverse reactions of the patients were compared and analyzed. The treatment group had better short- and long-term therapeutic efficacy compared to the control group, but no significant differences were observed between the two therapeutic regimens in adverse reactions. Elderly and advanced LSCC patients had worse therapeutic efficacy and a high probability of adverse reactions after the therapy. Collectively, our analysis data demonstrated that the bronchoscopic intratumoral injection of endostar and cisplatin had improved therapeutic efficacy, and the cardiovascular adverse reactions were within the controllable range in the treatment of LSCC in clinical practices.