IgA nephropathy (IgAN), the most common form of glomerulonephritis worldwide, often progresses to chronic kidney failure within 10 to 15 years. Despite its clinical importance, effective disease-modifying therapies for IgAN remain limited. Proteinuria is well recognized as both a prognostic biomarker and a modifiable therapeutic target in IgAN. Several randomized controlled trials conducted among Chinese patients with IgAN have demonstrated the efficacy of hydroxychloroquine (HCQ) in reducing proteinuria. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines also suggest that HCQ may exert potential therapeutic effects in IgAN. However, the molecular mechanisms underlying the renoprotective effects of HCQ remain incompletely understood. This review synthesises current evidence on HCQ's therapeutic mechanisms in IgAN, highlighting its multifaceted roles in: (1) suppressing pathogenic galactose-deficient IgA1 synthesis through modulation of mucosal immunity, Toll-like receptor (TLR) signaling, IL-6 pathways, and complement activation; (2) inhibiting autophagy-mediated antigen presentation via major histocompatibility complex class II (MHC-II) molecules; (3) modulating non-canonical autophagy pathways to attenuate human mesangial cells (HMCs) proliferation and protect podocytes; and (4) demonstrating antithrombotic effects. Collectively, HCQ demonstrates multifaceted mechanisms for proteinuria reduction in IgAN while maintaining a favorable safety profile.