Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. LINC00519 plays a prominent role in the progression of numerous cancers. To explore the molecular mechanism of LINC00519 in ICC, the expressions of LINC00519, hsa-miR-22-3p, and MECOM in ICC were assessed using the ENCORI database and qRT-PCR. The biological functions of LINC00519 in ICC were examined using a clone formation experiment, Transwell analysis, flow cytometry, and Western blot. Meanwhile, the mechanism of LINC00519 in ICC was determined by a dual-luciferase reporter assay. Results showed that LINC00519 and MECOM were highly expressed in ICC, whereas hsa-miR-22-3p was decreased. Functionally, silencing LINC00519 weakened ICC cell proliferation and migration and induced cell apoptosis. Also, LINC00519 knockdown repressed the PI3K/AKT (protein kinase B) pathway. Mechanistically, LINC00519 acted as a competitive endogenous RNA to target MECOM by sponging hsa-miR-22-3p. Meanwhile, rescue assays further proved that low LINC00519 expression restrained ICC cell proliferation and migration and accelerated apoptosis through the PI3K/AKT pathway by miR-22-3p/MECOM. In conclusion, this research revealed a novel LINC00519/hsa-miR-22-3p/MECOM regulatory axis and PI3K/AKT pathway that modulated ICC progression. This study deepens the understanding of the noncoding RNA regulatory network in ICC and provides potential targets for the diagnosis and targeted therapy of ICC.