<p>OLMALINC has functions in several cancers; however, its function in small cell lung cancer (SCLC) cells and the possible regulatory mechanism are not well understood. Here, we identified the prognostic value of OLMALINC for SCLC and its role in SCLC progression. To identify the expression level of OLMALINC in SCLC, we performed quantitative real-time PCR (RT-PCR) assays in SCLC and adjacent tissue samples. To assess the prognostic potential of OLMALINC, Kaplan-Meier/log-rank tests, Multivariate Cox regression analyses, and time-dependent receiver operating characteristic curves were undertaken. To explore the cell function of OLMALINC in SCLC cells, OLMALINC was inhibited or overexpressed in vitro cell models, followed by apoptosis detection, invasion/migration tests, and determination of neuroendocrine markers (GRP and calcitonin). To identify the possible downstream targets, bioinformatics prediction, analyses of expression level correlation, RIP, RNA pull-down assays, and recovery experiments were conducted. A consistent upregulation of OLMALINC was observed in tumor tissues of SCLC patients and cell lines. OLMALINC upregulation was related to advanced AJCC or VALSG stage, poor overall survival, and poor recurrence-free survival. Gain/loss of function studies of OLMALINC in SCLC cell lines showed OLMALINC decreased cell apoptosis but increased cell migration/invasion and levels of GRP and calcitonin. OLMALINC interacted with SMARCA4, thus activating EZH2. OLMALINC modulated H3K27me3 of CCL2 to regulate CCL2 expression levels. OLMALINC can predict SCLC prognosis and promote SCLC progression.</p>