Abstract: Objective To explore the effect of silencing lumican on the invasion and migration of liver cancer cells. Methods Lumican was silenced by shRNA in liver cancer cells (HepG2 and MHCC97H). The mRNA levels of lumican were detected by qRT-PCR. Cell invasion was measured by Transwell. Cell migration was tested via wound healing. The protein levels of lumican, MMP-9, VEGF, ERK1, JNK, p-ERK1 and p-JNK were measured by Western blot. Results Liver cancer cells (HepG2 and MHCC97H) had higher levels of mRNA and protein of lumican compared with normal hepatocyte L02 (P<0.01). shRNA lowered the levels of mRNA and protein of lumican (P<0.01), and weakened the invasion and migration of cancer cells (P<0.01). The expressions of MMP-9 and VEGF decreased with the shRNA silence (P<0.01). shRNA also reduced the protein level of p-ERK1 and p-JNK (P<0.01). Conclusion Silencing lumican by shRNA attenuates the invasion and migration of liver cancer cells via inhibiting the activation of ERK1/JNK pathway.