Objective To explore the molecular mechanism of LINC00626 regulating malignant progression of lung adenocarcinoma metastasis through JAK1/STAT3/KHSRP axis. Methods Quantitative real-time polymerase chain polymerase chain reaction was used to detect the expression of LINC00626 and KHSRP mRNA in human non-small-cell lung carcinoma cell lines (A549, H1299, H1975, H1437), human normal bronchial epithelial cell line (16HBE) and 144 lung adenocarcinoma tissues. The knockdown LINC00626 lentivirus and the control lentivirus were transferred into H1299 and H1437 cells, and named as sh-LINC00626 group (silencing of LINC00626 by transfecting short hairpin RNA lentiviral vector and sh-NC Group negative control by transfecting short hairpin RNA lentiviral). The overexpressed LINC00626 lentivirus and the control lentivirus were transferred into A549 and H1975 cells and named as LINC00626 group and Vector group. KHSRP vector on the basis of silencing LINC00626 and blank vector on the basis of silencing LINC00626 were added in H1437 cells. Cell counting kit-8 assay and Transwell migration/invasion assay were used to detect cell proliferation, migration and invasion. The expression levels of JAK/STAT and KHSRP in stably transfected cells were detected by Western blot. The effect of LINC00626 in vivo was studied in nude mice. Nuclear-cytoplasmic separation and RNA fluorescence in situ hybridization assay are used to predict the subcellular localization of LINC00626 and KHSRP. RNA pull down and mass spectrometry analysis were used to identify LINC00626 binding proteins. Results The expression levels of LINC00626 and KHSRP in non-small-cell lung carcinoma cell lines were significantly higher than those in normal human bronchial epithelial cells. LINC00626 and KHSRP were highly expressed in lung adenocarcinoma. Compared with the control group, the cell proliferation rate, colony formation, cell migration and invasion of H1437 cells were significantly decreased in knockdown group, while the reverse was true for over-expression. LINC00626 and KHSRP were located in the nucleus. LINC00626 directly binded to the KHSRP protein. Compared with the control group, H1437 cells transfected with knockdown LINC00626 and KHSRP significantly increased cell proliferation rate, cell migration, number of invasions. Compared with the control group, knockdown group showed a significant decrease in tumor volume and weight, cell proliferation rate and proliferation index, and the number of lung metastases. While the overexpression group showed an opposite effect, there were significant differences among the groups (P<0.01). The expression of JAK1 and STAT3 mRNA and protein in sh-LINC00626 group was lower than that in sh-NC Group (P<0.05), and the expression of JAK1 and STAT3 mRNA and protein in sh-LINC00626 group was higher than that in Vector group (P<0.05). Conclusion LINC00626 promotes malignant progression of lung adenocarcinoma metastasis through JAK1/STAT3/KHSRP signaling axis.