The study of lung cancer genome is an indispensable basis for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, the dysregulation of long-range chromatin interactions in lung cancer has been poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we generated high-resolution data revealing chromatin interactions associated with RNAPII (RNA Polymerase II), CTCF (CCCTC-binding factor), EZH2 (Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit), and H3K27me3 (Histone 3 lysine 27 trimethylation) by using specific antibodies with the long-read ChIA-PET (Chromatin interaction analysis by paired-end tag sequencing) method. EZH2/H3K27me3-mediated interactions are found to further silence target genes, either through loops or domains, and have distributions along the genome that are distinct from and complementary to those associated with RNAPII. We found that cancer-related genes are highly enriched in chromatin interactions. We identified abnormal interactions on oncogenes and tumor suppressors, such as additional repressive interactions on FOXO4 and promoter-promoter interactions between NF1 and RNF135. The knock-out of the abnormal interaction can reverse the dysregulation of cancer-related genes, which suggest that chromatin interactions are essential for proper expression of lung cancer-related genes. These findings provide a 3D landscape and gene regulatory relationship of lung cancer genome.