Objective To study the correlations between the levels of microRNA-223 (miR-223) and NOD-like receptor protein 3 (NLRP3) and renal interstitial fibrosis (RIF) in patients with IgA nephropathy (IgAN).Methods From January 2018 to January 2020, 164 patients with primary IgAN diagnosed via renal histopathology were selected. According to the degree of RIF, they were divided into RIF T0 group, RIF T1 group and RIF T2 group. In addition, 95 healthy volunteers during the same period were selected as the control group A and 80 patients with non-IgA nephropathy as the control group B. The general data of the subjects were compared among the groups. The mRNA expression levels of miR-223 and NLRP3 were measured via quantitative real-time polymerase chain reaction (qRT-PCR), while the levels of RIF-related indexes [transforming growth factor β₁ (TGF-β₁), monocyte chemoattractant protein (MCP-1), transforming growth factor α (TGF-α), interleukin-6 (IL-6), and hypoxia-inducible factor α (HIF-α)] were measured via enzyme-linked immunosorbent assay (ELISA). The Spearman method was used to analyze the correlations between the mRNA levels of miR-223 and NLRP3 and RIF-related indexes.Results Compared with control group A, the mRNA levels of miR-223 were lower in control group B, RIF T0 group, RIF T1 group and RIF T2 group and decreased successively in these groups (P < 0.05), while the mRNA levels of NLRP3, TGF-β1, MCP-1, TGF-α, IL-6 and HIF-α were higher and increased successively in these groups (P < 0.05). Spearman analysis showed that the levels of TGF-β1, MCP-1, TGF-α, IL-6 and HIF-α were negatively correlated with the mRNA level of miR-223, but were positively correlated with the mRNA level of NLRP3 in IgAN patients (all P < 0.05).Conclusions The miR-223 is lowly expressed in the serum of patients with IgAN, and is negatively correlated with RIF-related indexes. On the contrary, the NLRP3 is highly expressed and positively correlated with RIF-related indexes. Thus, miR-223 and NLRP3 may be involved in the progression of RIF in IgAN patients.