The lowered expression of HIF-1α and elevated expression of VHL in gallbladder adenocarcinoma are important markers for the progression, clinical biological behavior, and prognosis. Measurement of VHL and HIF-1α expression could be a tool for early detection of gallbladder cancer in benign lesions and in population screening. The highly inconsistent expression of VHL and HIF-1α in gallbladder may require further study to see whether they are intrinsically related.