Objective To explore the molecular mechanism by which miR-146b-5p promoted the malignant phenotype of esophageal squamous cell carcinoma(ESCC).Methods The cancer tissue and adjacent nor-mal tissue(NAT)samples from 38 patients with ESCC who underwent radical esophageal cancer treat-ment at the hospital from October 2020 to December 2021 were selected,and the expression of miR-146b-5p was detected using an in situ hybridization kit.Knockdown the expression of miR-146b-5p was achieved through siRNA transfection,and ensuing cellular changes of cellular behavior phenotype were evaluated through EdU and wound healing assay;Bioinformatics analysis predicted that CD82 was one of down-stream targets of miR-146b-5p;expression variation of CD82 was examined by Western blot;Dual lucifer-ase reporter assays was adopted to confirm the regulation between miR-146b-5p and target genes.Results The results of in situ hybridization assay showed that miR-146b-5p was highly expressed in ESCC tissues com-pared to the pathological score of NAT group(P<0.05);The EdU assay results showed that the KD group had a significant decrease in the proportion of EdU positive cells compared with the NC group(P<0.05).The results of the wound healing assay showed that KD group had a significant decrease in the pro-portion of wound healing compared with the NC group(P<0.05).The ENCORI database predicted that CD82 was a downstream target gene of miR-146b-5p.The Western-blot results showed that CD82 was sig-nificantly upregulated at protein level in KD group compared to NC group.The results of the dual lucifer-ase reporter assay showed that the fluorescence intensity of wt+mimic group was significantly reduced compared to mut+mimic group(P<0.05).Conclusion miR-146b-5p promotes the malignant phenotype of esophageal squamous cell carcinoma cells via CD82,and it will provide a new target for treatment of esophageal squamous cell carcinoma.