Objective To identify the relationship among glycogenes,N-glycans and hepatocarcinoma metastasis and drug resistance by studying the differential expressions of glycogenes and N-glycans in MHCC97-H and MHCC97-L human hepatocarcinoma cell lines,and to confirm the novel target of hepatocarcinoma metastasis and anti-tumor therapy.Methods Real-time PCR was used to quantitatively analyze glycogenes and fluorescein isothiocyanate (FITC)-lectin was used to analyze glycans characteristics.RNA interference approach was used to interfere the glycogenes,and the invasive ability in vitro and drug susceptibility of MHCC97-H cells were detected before and after interference.Modification of N-glycosylation (tunicamycin and PNGase F treatment) was done,and the invasiveness in vitro,tumorigenicity in vivo and drug susceptibility of MHCC97-H cells were detected before and after modification.Results The expressions of glycogenes and glycans were different in MHCC97-H cells and MHCC97-L cells.The silence of MGAT5 in MHCC97-H cells inhibited invasion ability and increased sensitivity to 5-fluorouracil in vitro(t =7.312,P ＜ 0.05).Modification of N-glycosylation decreased MHCC997-H cells invasion ability in vitro and tumorigenicity in vivo and increased sensitivity to 5-fluorouracil.Conclusion The differential expressions of glycogens and N-glycans in human hepatocarcinoma cell lines correlate with tumor invasion and drug resistance,and they are expected to be novel targets of tumor chemotherapy.