Objective Cisplatin (DDP) is widely used in the chemotherapy of lung cancer. However, cisplatin resistance represents a major obstacle in its effective treatment. Our preliminary work has demonstrated that inactivated Sendai virus (HVJ-E) shows that it induces apoptosis in murine melanoma cells (B16) and obviously inhibites the tumor growth in tumor-bearing BALB/ c nude mice. This study aims to investigate whether inactivated HVJ-E has an effect of inducing apoptosis in cisplatin-resistant A549/ DDP lung adenocarcinoma cells in vitro and in vivo. Methods HVJ-E and A549/ DDP cells were co-cultured in vitro, and the effect of HVJ-E on the apoptosis in A549/ DDP cells was detected by flow cytometry. In addition, HVJ-E was injected into the tumor in vivo, and its oncolytic effect was observed by TUNEL assay of tissue sections and measurement of tumor size. Results After co-cultured with HVJ-E for 12 h, 24 h and 36 h, the apoptosis rate of A549/ DDP cells in late stage detected by flow cytometry was 7.7%, 12.6% and 18.9%, respectively, showing a significant difference between 12 h and 24 h, and between 24 h and 36 h. TUNEL assay showed that there was more apoptosis in tumor cells in vivo in the experimental group than in the control group. Meanwhile, intratumoral injection of HVJ-E induced a significantly smaller tumor volume in the experimental group compared with the control group ( P ﹤ 0.05). Conclusions Our findings indicate that inactivated HVJ-E can induce apoptosis in A549/ DDP cells both in vitro and in vivo, and intratumoral injection of inactivated Sendai virus significantly reduces the tumor growth in vivo.