Glioblastoma is the most aggressive primary brain tumors originated from the glial cells in adults, which is characterized by stronger migration and invasion. Paclitaxel is an efficient anti-glioblastoma drug for patients in clinical. However, potential molecular mechanism of paclitaxel-inhibited growth and proliferation of glioblastoma has not been well understood yet. In this study, we investigated signal pathway mediated by paclitaxel in glioblastoma cells. Our results demonstrated that paclitaxel treatment inhibited growth and proliferation of glioblastoma cell line U251. Paclitaxel administration induced apoptosis of U251 cells by up-regulation of caspase signal pathway. Mechanism analyses showed that paclitaxel addition down-regulated MMP-9 expression, which further inhibited p38/JNK signaling pathway in U251 cells. In vivo assays showed that Paclitaxel treatment could significantly inhibit glioblastoma growth and prolong survival of tumor-bearing mice. In conclusion, these results indicate Paclitaxel administration inhibits growth and proliferation of glioblastoma through MMP-9-meidated p38/JNK signaling pathway, which contributes to understanding signal pathway of paclitaxelsuppressed glioblastoma growth.