Medulloblastoma is the most frequent pediatric brain tumor, with the capacities of rapid proliferation and intracranial dissemination. However, the factor(s) regulating medulloblastoma growth has not yet been well characterized. Leukemia-inhibitory factor (LIF) and interleukin-6 (IL-6) play different roles in the formation/progression of various embryonic and pediatric tumors, but their biological effects on medulloblastoma cells are less well known. Therefore, in vivo and in vitro expression of LIF, IL-6 and their signal transducer genes encoding LIF receptor (LIFR), IL-6 receptor (IL-6R) and gp130 in human medulloblastoma cells were investigated by multiple cellular and molecular biology approaches. The results revealed that LIF expression could be found in 26 out of 28 tumors/cell line and over 90% of the samples expressed LIFR, IL-6R and gp130. In contrast, none of the samples showed IL-6 expression. An established medulloblastoma cell line, Med-3, was used to evaluate the potential effects of LIF and IL-6 on the proliferation of medulloblastoma cells. The growth of Med-3 cells was efficiently inhibited either by anti-LIF antibody or by antisense LIF oligonucleotide. Addition of exogenous human recombinant IL-6 could dramatically enhance Med-3 cell outgrowth. Our data thus for the first time demonstrated the important role of LIF as an autocrinal and IL-6 as a paracrinal growth factor in the proliferation of medulloblastoma cells.