Many studies have been reported that tripartite motif-containing (TRIM) proteins play important roles in various cellular processes and involved in many diseases. TRIM3, a member of TRIM family, has been proved that it plays important roles in various cancers. Nevertheless, its effects on cervical cancer reminded unknown. This study aimed to explore TRIM3 function in cervical cancer cells. The results of quantitative real-time RT-PCR and western blotting showed that the TRIM3 expression was very low in five cervical cancer cell lines. The TRIM3 overexpression weakened cell viability, and promote apoptosis of C-33A and SiHa cells in vitro, and inhibit tumor growth in vivo, which suggested that TRIM3 could reduce proliferation of cervical cancer cells. Moreover, TRIM3 up-regulation enhanced caspase-3 activity and increased the expressions of cleaved caspase-3 and p53, at the same time decreased p38 phosphorylation level. In addition, TRIM3 down-regulation had opposite effects on cell proliferation and expressions of the three proteins, which could be suppressed by p38-specific inhibitor (58203580). In conclusion, TRIM3 had the ability to suppress cell proliferation by inactivating p38 signaling pathway, which indicated that it might act as a tumor inhibitor and an underlying therapeutic target for cervical cancer. (C) 2018 Elsevier Inc. All rights reserved.