Objective To investigate the association of calcium-activated neutral protease 1（CAPN1）with the invasion and me-tastasis of oral squamous cell carcinoma（OSCC）cells. Methods The immortalized normal oral epithelial cell line HOK was selected as control（normal group），and the OSCC cell lines HSC3 and CAL27，with different origins，were selected for the experiment（tumor group）. Western blot was used to measure the expression of CAPN1 in the normal group and the tumor group. Two groups of HSC3 and CAL27 cells in OSCC cell line were used as research subjects and were randomly divided into siRNA1-1 group（siRNA CAPN1-1 was transfected into the two groups of OSCC cells），siRNA1-2 group（siRNA CAPN1-2 was transfected into the two groups of OSCC cells）， and siRNA-neg group（non-specific siRNA [siNC] was transfected into the two groups of OSCC cells as control group）. PCR and West-ern blot were used to measure the changes in the mRNA and protein expression levels of CAPN1 in cells after transfection. Transwell chamber was used to design the migration and invasion experiment of tumor cells to observe the changes in the migration and invasion abilities of cells after transfection. Results Western blot showed that the expression of CAPN1 in the tumor group was significantly high-er than that in the normal group（P < 0.05）. PCR and Western blot showed that for HSC3 and CAL27 cells，the siRNA1-1 group and the siRNA1-2 group had significant inhibition of the mRNA expression of CAPN1 compared with the siRNA-neg group（P < 0.05）. Transwell chamber assay showed that compared with the siRNA-neg group，the siRNA1-1 group and the siRNA1-2 group had signifi-cant reductions in migration and invasion abilities and the number of membrane penetration（P < 0.01，P < 0.05）. Conclusion CAPN1 can increasethemigrationandinvasionabilitiesofOSCCcellsandmayplayanimportantroleinthedevelopmentandprogressionofOSCC.