Introduction: Huge amounts of gene-sequencing data have been used to guide fundamental researches. The study combined bioinformatics tools with basic study to analyze the pathological mechanisms of diffuse large B-cell lymphoma. Methods: A LncRNA-miRNA-mRNA ceRNA network of diffuse large B cell lymphoma was constructed by GTEx combined with TCGA database analysis. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. The proteins levels of UPR sensors, GRP78, p-IRE1α, IRE1α, active ATF6, ATF4 and XBP1, were assessed through Western blot, along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62) after LINC00963 overexpression or miR-320a overexpression in vitro. Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay. Results: Evaluation of SUDHL4 cell showed marked up-regulation of key elements of the UPR (GRP78, p-IRE1α, spliced XBP-1(XBP-1(s))), apoptosis (Bax, cleaved caspase 3) and autophagy (Beclin1, LC3II) after LINC00963 overexpression in vitro, whereas miR-320a mimic reversed the effects. Besides, LINC00963 targeted miR-320a while miR-320a bound to the 3’UTR of XBP1. The work also found that LINC00963 overexpression resulted in significant tumor growth delay in a xenograft model of DLBCL. Conclusion: Mechanistically, LINC00963 / miR-320a regulated XBP1-apoptosis pathway and autophagy, making this pathway an attractive therapeutic target for selective targeting. The data presented here are the first to comprehensively survey the mechanism of LINC00963 / miR-320a/XBP1 in DLBCL.