In　this　study,　inexpensive,　environmentally　friendly,　and　biodegradable　cellulose　filter　paper　was　used　to　load　nano　zero-valent　iron　(nZVI),　effectively　improving　the　dispersibility　of　nZVI　and　successfully　preparing　the　supported　modified　cellulose　filter　paper　(FP-nZVI).　Subsequently,　the　capacity　of　FP-nZVI　to　remove　Cr(VI)　in　a　flow　system　was　explored.　FP-nZVI　was　characterized　by　scanning　electron　microscopy　(SEM),　Fourier　transform　infrared　spectroscopy　(FTIR),　and　X-ray　diffraction　(XRD).　Traditional　single-factor　experiments　often　require　a　large　number　of　repeated　experiments　when　analyzing　the　interactions　among　multiple　variables,　resulting　in　a　long　experimental　cycle　and　high　consumption　of　experimental　materials.　This　research　used　the　Response　Surface　Methodology　(RSM)　based　on　the　Box-Behnken　Design　(BBD)　and　the　Artificial　Neural　Network　(ANN)　to　optimize　and　predict　the　removal　process　of　Cr(VI).　This　RSM　investigated　the　interactions　between　the　response　variable　(Cr(VI)　removal　rate)　and　the　independent　variables　(Cr(VI)　concentration,　pH　value,　and　flow　rate).　A　highly　significant　quadratic　regression　model　was　constructed,　which　was　proven　by　a　high　F　value　(93.92),　an　extremely　low　p-value　(＜0.0001),　and　a　high　determination　coefficient　(R-2　=　0.9918).　An　ANN　model　was　established　to　forecast　the　correlation　between　independent　variables　and　the　removal　rate　of　Cr(VI).　Both　models　demonstrate　remarkable　consistency　with　the　experimental　data;　however,　from　the　perspective　of　statistical　parameters,　the　ANN　model　has　more　significant　advantages;　the　coefficient　of　determination　R-2　reaches　0.9937,　which　is　higher　than　that　of　RSM　(0.9918);　the　values　of　indicators　such　as　MSE,　RMSE,　MAE,　MAPE,　AAD,　and　SEP　are　all　smaller　than　those　of　RSM.　The　ANN　exhibits　greater　excellence　in　prediction　error,　value　fluctuation,　and　closeness　to　the　actual　value　and　has　a　more　excellent　prediction　ability.　The　experiment　for　treating　Cr(VI)　with　FP-nZVI　was　optimized,　achieving　good　results.　Meanwhile,　it　also　provides　a　valuable　reference　for　similar　experimental　studies.