Background: It has been extensively reported that long noncoding RNAs (lncRNAs) were closely associated with multiple malignancies. However, as an important lncRNA, POU6F2-AS1 (POU6F2-antisense 1) is little known in lung adenocarcinoma (LADC). We therefore performed this study to examine the effects and mechanism of POU6F2-AS1 in LADC. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets provided us clinical samples of LADC. QRT-PCR and western blotting were conducted to reveal the expression level of POU6F2-AS1 and KCNJ4. Four LADC cell lines were used in this exploration. Cell proliferation, colony formation, invasion and migration of LADC cells were detected using Cell Counting Kit-8 (CCK-8) assay, colony formation analysis and transwell assays, respectively. Online prediction, luciferase reporter assay and rescue experiments determined the correlation between miR-34c-5p and POU6F2-AS1 or KCNJ4. Results: High-regulation of POU6F2-AS1 was found in LADC tissues compared with normal tissues, which correlated with poor outcome of LADC patients. Functional experiments showed that POU6F2-AS1 significantly promoted cell proliferation, colony formation, invasion and migration using Calu-3 cells and NCI-H460 cells. POU6F2-AS1 acted as a competing endogenous RNA (ceRNA) of miR-34c-5p and facilitated the expression of KCNJ4 (potassium voltage-gated channel subfamily J member 4). The promoted influence of cell aggressiveness by POU6F2-AS1 was contributed by KCNJ4, whilst was abrogated by miR-34c-5p. Conclusion: In conclusion, POU6F2-AS1 functioned as a ceRNA through sponging miR-34c-5p to high-regulate KCNJ4 in LADC, which indicated that POU6F2-AS1 might play a promising therapeutic target and a potential prognostic biomarker for LADC treatment.