Abnormal expression of long noncoding RNA (lncRNA) is involved in human cancers, including colorectal cancer (CRC). However, their functional mechanism is largely unknown. In this study, we explored the roles of lncRNA SOCS2-AS1 in modulating CRC progression. We showed that SOCS2-AS1 was lowly expressed in CRC tissues and cells. SOCS2-AS1 downregulation predicted a poor prognosis in patients with CRC. SOCS2-AS1 overexpression significantly suppressed CRC cell proliferation, colony formation, EdU incorporation, cell-cycle, migration and invasion in vitro while SOCS2-AS1 knockdown led to an opposite phenotype. SOCS2-AS1 overexpression inhibited CRC growth and metastasis in vivo. Mechanistically, we discovered that SOCS2-AS1 was positively correlated with SOCS2 expression in CRC tissues. SOCS2-AS1 contributes to SOCS2 expression through restraining miR-1264. Additionally, we showed that SOCS2 silencing abrogated the suppressive effects of SOCS2-AS1 overexpression. Taken together, our results identified a novel regulatory loop in which SOCS2-AS1/miR-1264/SOCS2 axis suppresses CRC progression.