As a Gram-positive cocci existing in nature, Staphylococcus has a variety of species, such as Staphylococcus aureus and Staphylococcus epidermidis, etc. Growing evidence reveals that Staphylococcus is closely related to the occurrence and development of various cancers. On the one hand, cancer patients are more likely to suffer from bacterial infection and antibiotic-resistant strain infection compared to healthy controls. On the other hand, there exists an association between staphylococcal infection and carcinogenesis. Staphylococcus often plays a pathogenic role and evades the host immune system through surface adhesion molecules, α-hemolysin, PVL (Panton-Valentine leukocidin), SEs (staphylococcal enterotoxins), SpA (staphylococcal protein A), TSST-1 (Toxic shock syndrom toxin-1) and other factors. Staphylococcal nucleases (SNases) are extracellular nucleases that serve as genomic markers for Staphylococcus aureus. Interestingly, a human homologue of SNases, SND1 (staphylococcal nuclease and Tudor domain-containing 1), has been recognized as an oncoprotein. This review is the first to summarize the reported basic and clinical evidence on staphylococci and neoplasms. Investigations on the correlation between Staphylococcus and the occurrence, development, diagnosis and treatment of breast, skin, oral, colon and other cancers, are made from the perspectives of various virulence factors and SND1.