This study provides a comprehensive genomic and epigenomic characterization of lung squamous cell carcinomas (SQCCs) as part of The Cancer Genome Atlas (TCGA) project. The analysis includes 178 histopathologically reviewed lung SQCCs, with additional whole-genome sequencing and microRNA sequencing data. The tumors display a high overall mutation rate of 8.1 mutations per megabase and complex genomic alterations, including 360 exonic mutations, 323 copy number segments, and 165 genomic rearrangements per tumor. Statistically recurrent mutations were identified in 11 genes, including *TP53*, which was mutated in nearly all specimens. Previously unreported loss-of-function mutations were found in the *HLA-A* class I major histocompatibility gene. Significantly altered pathways included *NFE2L2* and *KEAPI* in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and *CDKN2A* and *RBI* in 72% of tumors. The study identifies potential therapeutic targets in most tumors, offering new avenues for the treatment of lung SQCCs.This study provides a comprehensive genomic and epigenomic characterization of lung squamous cell carcinomas (SQCCs) as part of The Cancer Genome Atlas (TCGA) project. The analysis includes 178 histopathologically reviewed lung SQCCs, with additional whole-genome sequencing and microRNA sequencing data. The tumors display a high overall mutation rate of 8.1 mutations per megabase and complex genomic alterations, including 360 exonic mutations, 323 copy number segments, and 165 genomic rearrangements per tumor. Statistically recurrent mutations were identified in 11 genes, including *TP53*, which was mutated in nearly all specimens. Previously unreported loss-of-function mutations were found in the *HLA-A* class I major histocompatibility gene. Significantly altered pathways included *NFE2L2* and *KEAPI* in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and *CDKN2A* and *RBI* in 72% of tumors. The study identifies potential therapeutic targets in most tumors, offering new avenues for the treatment of lung SQCCs.