Background & Objective: The incidence of prostate cancer is increasing rapidly in China, and most patients are advanced cases when they were confirmed. Advanced prostate cancer is very difficult to control, although the patients could get transient recovery after total androgen blockade. Insulin-like growth factor II (IGF-II) can improve cell proliferation and inhibit cell apoptosis. Loss of imprinting (LOI) of IGF-II, or activation of the normally silent and maternally inherited allele, was discovered in some types of cancer. Our study was to explore the genomic imprinting of IGF-II in prostate cancer and its correlation to disease progression., Methods: LOI of IGF-II in 41 specimens of prostate cancer, 27 specimens of benign prostate hyperplasia, and 13 specimens of normal prostate tissue was detected by polymerase chain reaction-based restrictive fragment length polymorphism (PCR-RFLP) analysis., Results: Rates of heterozygote of IGF-II DNA were 70.7% (29/41) in prostate cancer group, 55.5% (15/27) in benign prostate hyperplasia group, and 61.5% (8/13) in normal prostate tissue group. In the specimens with IGF-II DNA heterozygote, the occurrence rate of LOI of IGF-II was significantly higher in prostate cancer than in benign prostate hyperplasia and normal prostate tissue (58.6% vs. 13.3% and 12.5%, P<0.05). LOI of IGF-II had no correlation to patients'age, serum level of prostate-specific antigen (PSA), presence of bone metastasis, and cell differentiation before endocrinotherapy. Received total androgen blockade, the 1-year progress-freely survival rate was significantly lower in the patients with LOI of IGF-II than in the patients without LOI of IGF-II (70% vs. 100%, P=0.039)., Conclusion: LOI of IGF-II occurred frequently in advanced prostate cancer, and maybe correlated to progression of prostate cancer after total androgen blockade.