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Objective: To explore the effects of miR-588 on the proliferation and migration of neuroblastoma（ NB） cells by regulating the expression of ubiquitin-specific protease 22 （USP22） and its mechanism. Methods: The targeting relationship between miR-588 and USP22 were verified by dual luciferase report. The SK-N-SH cells were divided into NC group, miR-588 group, miR-588+USP22 group and USP22 group. The levels of miR-588 mimic and/or USP22 were overexpressed by transfection of miR-588 mimic and/or USP22 plasmid. The level of USP22 mRNA and protein were detected by qPCR and Western blot respectively. The proliferation, migration and invasion abilities of each group were detected. The levels of tumor necrosis factor-α（ TNF-α） and soluble interleukin-2 receptor （sIL-2R） were detected by ELISA. Results: miR-588 could bind to the 3'-untranslated region （3'-UTR） of USP22 mRNA. The USP22 mRNA and protein in the miR-588 group were significantly lower than those in the NC group （P<0.05）. The levels of USP22 mRNA and protein in the miR-588+USP22 group were significantly higher than those of the miR-588 group and lower than those of the USP22 group （P<0.05）. Compared with the NC group, the proliferation, migration and invasion abilities of the miR-588 group were significantly increased （P<0.05）. The effects of USP22 were opposite to miR-588（P<0.05）. The proliferation, migration and invasion abilities of miR-588+USP22 group were significantly higher than those of the miR-588 group and lower than those of the USP22 group（ P<0.05）. Compared with the NC group, the levels of TNF-α［ （8.97±0.90） pg/ml］ and sIL-2R［ （6.68±0.75） pg/ml］ in the miR-588 group were significantly increased, while the TNF-α［ （2.04±0.31） pg/ml］ and sIL-2R［ （1.48±0.19） pg/ml］ levels in the USP22 group were significantly reduced（ P<0.05）. The levels of TNF-α［ （4.16±0.49） pg/ml］ and sIL-2R［ （3.21±0.41） pg/ml］ in the miR-588+USP22 group were significantly lower than those in the miR-588 group and higher than those in the USP22 group （P<0.05）. Conclusion: miR-588 can induce the secretion of TNF-α and sIL-2R by targeting the expression of USP22, thereby alleviating immunosuppression, and inhibiting the proliferation and metastasis of NB cells. [ABSTRACT FROM AUTHOR]