During active transcription and replication chromatin architecture is altered, allowing formation of DNA secondary structures. G-quadruplexes (G4s) have emerged as important regulatory DNA structures and have been associated with genomic instability, genetic diseases and cancer progression. Experimental evidence for G4 prevalence in the entire human genome is still lacking. We present a high-resolution sequencing-based method that detected 716,310 distinct G4s in the human genome, more than predicted by computational methods, including structural variants previously uncharacterised in a genomic context. We observed high G4-density in functional regions, such as 5’ UTRs and splicing sites, and in genes not predicted to have such structures (BRCA1 and BRCA2). We found a significant association of G4 formation with oncogenes and tumor suppressors, and with Somatic Copy-Number Alterations (SCNAs) that act as cancer drivers. Our results support that G4s are promising targets for cancer intervention and suggest novel candidates for further biological and mechanistic studies.