〔Abstract〕 Abstract Objective To investigate the effect and mechanism of sex-determining region Y-box transcription factor 4 (SOX4) on autophagy in small cell lung cancer (SCLC) cells . Methods Human SCLC cell line NCI-H446 was transfected with small interfering RNA ( siRNA) to knockdown SOX4 . RT-qPCR and Western blot were used to verify the transfection efficiency . NCI-H446 cells were divided into control group , si-SOX4 group , si-SOX4 + oe- Beclin1 group and oe-Beclin1 group . Western blot analysis was performed to detect the ratio of microtubule-associ- ated protein 1 light chain 3 (LC3)-Ⅱ/LC3 - Ⅰ expression and the expression of Beclin1 and p62 in different groups of cells . The transcriptional regulation of Beclin1 by SOX4 was detected by dual luciferase reporter assay and chro- matin immunoprecipitation PCR ( ChIP-PCR) assay . CCK-8 assay was used to detect the proliferation ability of NCI-H446 cells in different groups . Flow cytometry was used to detect the apoptosis rate of NCI-H446 cells in dif- ferent groups . Transwell assay was performed to determine the cell migration and invasion ability in different groups . Results Compared with the control group or the si-NC group , the relative mRNA and protein expression level of SOX4 in si-SOX4 group were down-regulated (P < 0. 05) , and the ratio of LC3-Ⅱ/LC3 - Ⅰ protein expres- sion and the relative protein expression level of Beclin1 in si-SOX4 group decreased (P < 0. 05) , the relative pro- tein expression of p62 increased (P < 0. 05) . The relative luciferase activity of Beclin1 WT in the si-SOX4 group was lower than that in the si-NC group (P < 0. 05) ; the relative enrichment of Beclin1 promoter in the Anti-SOX4 group was higher than that in the Anti-IgG group (P < 0. 05) . Compared with control group , cell proliferation ac- tivity decreased , cell apoptosis rate increased , migration number and invasion number decreased in si-SOX4 group (P < 0. 05) . Compared with the si-SOX4 group , the ratio of LC3-Ⅱ/LC3 - Ⅰ protein expression and the relative protein expression of Beclin1 increased in si-SOX4 + oe-Beclin1 group , while the relative protein expression of p62 decreased , cell proliferation activity increased , apoptosis rate decreased , migration number and invasion number increased (P < 0. 05) . Conclusion Down-regulation of SOX4 can inhibit autophagy , decrease proliferation activi- ty of NCI-H446 cells , and inhibit cell migration and invasion by inhibiting Beclin1 expression .