We report a portable and highly sensitive Hg2+nanosensor, where the CuS nanozyme functions as an Hg2+recognition unit, a Hg2+enrichment/preconcentration carrier, and a signal amplifier/output unit. The as-designed enrichment-detection integration strategy is customizable and endows the sensor with both a wide detection range from 50 ppt to 400 ppb and a high sensitivity with a minimum detectable Hg2+concentration of 50 ppt. In order to make the Hg2+nanosensor portable and cost-effective, a commercial RGB sensor is employed here in conjunction with the Hg2+-dependent colorimetric reaction. More importantly, the as-developed Hg2+nanosensor is feasible for analysis of real samples with satisfactory accuracy (deviation <10%) and reproducibility (recovery ∼82%). Thus, this portable Hg2+nanosensor appears to be a viable solution to meet the actual needs of on-site and real-time mercury contamination analysis and may also pave the way to colorimetric nanosensors for other metal ions.