Wingless and int homologue (Wnt) family proteins have been shown to have important roles in the decision of cell fate and behavior at multiple stages during the development and tumorigenesis. One of the Drosophila segment polarity genes, porcupine (porc) gene, encodes an evolutionarily conserved endoplasmic reticulum membrane protein involving in the post-translational processing of the Wnt family proteins. Here, we report that human homologue of Drosophila porc gene, PPN/MG61, was abundantly expressed in human cancer cell lines, but not in normal cells. We also found that PPN/MG61 was overexpressed in primary lung cancer tissue samples, compared to their matched normal tissue samples. Furthermore, when we used small interfering RNA to knock down PPN/MG61 mRNA in lung cancer cells expressing the gene, we observed apoptosis induction, along with decreased activity of Wnt pathway in those lung cancer cells. These data suggest that PPN/MG61 may be a novel marker for human lung cancer and that post-translational modification of the Wnt signal molecules by PPN/MG61 may be important for the function of Wnt pathway in lung cancer.