Rapid, efficient, and selective separation of tumor cells from complex body fluids is urgently needed for clinical application of tumor-cell-based liquid biopsy. Herein, a size-selective affinity filtration system, named Selective, User-friendly, highly Porous, Efficient, and Rapid filter (SUPER Filter), was developed for high-performance tumor cell isolation and analysis. SUPER Filter enabled selective interaction of tumor cells with size-optimized and antibody-coated micropore walls during filtration, achieving high efficiency of 91.0 ± 6.1% in PBS and 83.7 ± 6.4% in whole blood. Meanwhile, its larger micropore size than traditional filtration devices greatly reduced nonspecific capture of background cells (55-126 cells/mL blood) with enrichment factors of 1.1 × 10⁴ - 1.0 × 10⁵ and purity of 52.7 ± 4.2%. Moreover, its high porosity enabled ultra-fast (< 5 s for 1 mL of blood or 10 mL of buffer samples) and user-friendly gravity-driven filtration. Finally, SUPER Filter demonstrated rapid, efficient, and selective separation of tumor cells from blood and large-volume pleural and ascetic fluid samples of cancer patients for morphological and molecular analysis. We expect that this size-selective affinity filtration strategy facilitates clinical application of tumor-cell-based liquid biopsy.