The ubiquitously expressed family of Id(inhibitor of differentiation) helix-loop-helix(HLH) proteins function as dominant negative regulators of basic HLH (bHLH) transcriptional regulators. In eukaryotic organisms, Id proteins have been implicated in development, cell differentiation, proliferation, angiogenesis, invasion and migration. Recent studies revealed that Id proteins are not only significantly correlated with cancer progression and prognosis, but also exploited as a tumor therapeutic target. The roles of Id proteins in tumorigenesis were reviewed and the opportunities of Id proteins in cancer targeted therapy were discussed.