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Background Surgical resection and local ablation are important curative treatments for hepatocellular carcinoma. However, the 5-year recurrence rate after ablation can reach 70%. Ablation-induced heat stress may contribute to recurrence by reshaping the tumor microenvironment. A better understanding of immune microenvironmental differences in recurrent hepatocellular carcinoma (RHCC) after different treatments is critical to develop strategies for recurrence prevention and precision treatment. We aimed to characterize the transcriptomic profile and immune microenvironment of RHCC after local ablation and surgical resection.Methods We performed integrative multi-omics profiling, including bulk RNA-seq, single-cell RNA-seq (scRNA-seq), spatial transcriptomics, and multiplex immunofluorescence (IF), in 36 RHCC samples with matched clinical features, comprising 18 ablation-related and 18 surgery-related cases.Results Based on bulk RNA sequencing, ablation-related RHCC was enriched in immunosuppressive pathways (i.e., immune escape signature, P=0.015), whereas surgery-related RHCC showed enrichment of metabolic pathways (i.e., propanoate metabolism). Immune cell infiltration analysis indicated an increased proportion of regulatory T cells (Tregs) in ablation-related recurrence.ScRNA-seq further demonstrated increased Tregs in ablation-related RHCC, mainly driven by expansion of TNFRSF18+CCR8+T follicular regulatory (Tfr)-like cells (P<0.05). Tfr-like cells exhibited higher expression of immune checkpoint molecules, increased immunosuppressive gene signatures and enrichment of the IL10 signaling pathway. Trajectory analysis and TCR clonotype sharing suggested that TNFRSF18+Tfr-like cells may originate from naive Tregs. Correlation analysis identified six cellular modules, one of which significantly expanded in ablation-related recurrence and contained tumor cells, TNFRSF18+ Tfr-like cells, and T follicular helper (Tfh) cells, a key component of tertiary lymphoid structures (TLS), sites of local anti-tumor immunity. Tfh cells displayed reduced expression of IL21 and ICOS(P<0.01), indicating impaired helper function. Cell–cell interaction analysis showed that Tfr-like cells suppressed Tfh function through IL10–IL10R signaling, leading to impaired anti-tumor immunity. Spatial transcriptomics and multiplexed IF confirmed the co-localization of Tfr-like and Tfh cells within lymphocyte-enriched aggregate regions, where neighboring CD8+ T cells exhibited reduced cytotoxic signatures, suggesting impaired anti-tumor immune responses.Conclusions Compared with surgery-related RHCC, ablation-related RHCC is characterized by Tfr-associated immunosuppressive microenvironment remodeling. Targeting Tfr-like cell-centric pathways, such as IL10–IL10R signaling, may restore Tfh function and improve anti-tumor immunity, providing potential strategies for preventing ablation-related recurrence.