Tailings　produced　in　the　beneficiation　of　Carlin-type　gold　deposits　are　characterized　by　fine　particle　size　and　high　mud　content.　When　neutralized　with　wasted　acid　generated　by　pressurized　pre-oxidation,　the　tailings　turn　to　neutralized　slag　and　perform　as　a　novel　backfill　material.　To　understand　the　influential　behavior　of　variable　factors　on　the　strength　and　its　optimization　of　cemented　neutralization　slag　backfill,　RMS-BBD　design　test　was　carried　out　with　56–60%　slurry　mass　fraction,　12.5–25%　cement/(neutralization　slag　+　waste　rock)　(i.e.,　C/(S+R))　and　30–40%　waste　rock　content.　A　modified　three-dimensional　quadratic　regression　model　was　proposed　to　predict　the　strength　of　cemented　neutralization　slag　backfill.　The　results　showed　that　backfill　strength　predicted　by　the　modified　ternary　quadratic　regression　model　was　in　high　coincidence　with　the　data　of　backfill　mixture　tests.　C/(S+R)　was　predominant　in　backfill　strength　with　regard　to　every　single　influential　factor　throughout　the　curing　age,　and　the　mass　fraction　of　slurry　had　a　significant　effect　on　the　later　strength.　From　the　perspective　of　economic　and　engineering　operation,　a　multi-objective　function　method　was　further　introduced　to　optimize　the　backfill　strength.　The　optimal　mixture　proportion　of　cemented　neutralized　slag　backfill　slurry　was:　58.4%　slurry　mass　fraction,　32.2%　waste　rock　content,　and　20.1%　C/(S+R).　The　backfill　strength　of　this　mixture　proportion　on　days　7,　28　and　56　was　verified　as　0.42,　0.64　and　0.85　MPa,　respectively.　RSM-BBD　design　and　multi-objective　function　optimization　proposed　a　reliable　way　to　evaluate　and　optimize　the　strength　of　neutralized　slag　backfill　with　high　mud　content.　©　2022　by　the　authors.　Licensee　MDPI,　Basel,　Switzerland.