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Hepatocellular carcinoma (HCC) is a major malignant tumor type with a high incidence and mortality. Infection with hepatitis virus is a high-risk factor. Previous studies have demonstrated that microRNA (miR)-223 was downregulated in HCC tissues. NOD-like receptor family, pyrin domain containing 3 (NLRP3)-is a potential target of miR-223 and has a vital role in hepatitis infection. The present study was performed to investigate the role of miR-223 in the proliferation and apoptosis of HCC cells through regulating NLRP3. A dual luciferase reporter assay was performed to confirm the direct interaction between miR-223-3p and the 3' untranslated region of NLRP3 mRNA. Hep3B cells were then transfected with miR-223 mimics and the proliferation and apoptosis were determined by an MTT and a flow cytometric assay, respectively. The expression of NLRP3 and caspase-1 was analyzed at the mRNA as well as at the protein level by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The secretion of interleukin (IL)-1β and IL-18 in the culture supernatants was measured by ELISA. The dual luciferase assay confirmed NLRP3 as a direct target of miR-223. Overexpression of miR-223 in hep3B cells significantly suppressed cell proliferation and promoted apoptosis. Furthermore, the expression of NLRP3 was downregulated by miR-223 transfection. Certain downstream factors of the NLRP3 pathway were also downregulated following overexpression of miR-223. Caspase-1 was decreased at the transcriptional level and the cleaved caspase-1 was decreased at the protein level. Secretion of IL-1β and IL-18 into the culture medium by cells transfected with miR-223 was lower than that by the control cells. In conclusion, the tumor suppressor role of miR-223 was associated with the regulation of NLRP3 inflammasome components. miR-223 inhibited HCC cell proliferation and promoted apoptosis by directly targeting NLRP3. Downstream production of caspase-1, IL-1β and IL-18 were also repressed by miR-223. These results provided insight into the association between the innate immune system and the genesis of HCC.