In this study, we have characterized a selected pseudogene-derived lncRNA PLEKHA8P1 that could function as a prognostic marker, promotes tumor progression and affects 5-FU-mediated chemoresistance through positive regulation of its parental gene PLEKHA8. Given our initial observations and known role of parental gene PLEKHA8 in tumorigenesis, we highlight the potential of PLEKHA8P1 as a novel therapeutic target in chemoresistance in liver cancer. The gene discussed is PLEKHA8; the disease is liver cancer.