8-nitroguanine (8-NG) is a mutagenic nitrative DNA/RNA lesion caused by reactive nitrogen species (RNS). As a modified nucleoside base, 8-NG is considered important because of its abundance and its mutagenic potential through G-to-T transversion mutations upon replication of DNA. 8-NG also participates in epigenetic regulation of gene activation/repression by causing breaks in DNA to form single-stranded DNA. It has also been demonstrated that increased concentrations of 8-NG are pathogenically linked to various inflammation-associated diseases, including cancer. Comparative urine/serum 8-NG assays mainly reflect the balance between nitrosative damage and the repair rate of the whole body. However, quantifying 8-NG content directly in different cells/tissues of normal/disease states allows tissue-specific nitrosative damage of DNA/RNA to be identified. Thus, this method provides more useful information about nitrosative damage-disease relationships to benefit disease diagnostics and therapeutics.