In this study, a novel automatic analytical methodology using a titanium dioxide (TiO₂)-assisted preconcentration/on-site vapor-generation (VG) chip hyphenated with inductively coupled plasma-mass spectrometry (ICP-MS) for online determination of mercuric ions (Hg²⁺) was developed. Interestingly, the TiO₂ nanoparticle (nano-TiO₂) coating on the channel surface acted not only as a sorbent for preconcentration but also as a catalyst for photocatalyst-assisted VG. Under optimum operation conditions, the developed method was validated by analyzing the certified reference material (CRM) Seronorm™ Trace Elements Urine L-2 (freeze-dried human urine). Based on the obtained results, the dramatic reduction of “hands-on” manipulation and the elimination of hazardous materials (e.g., sodium borohydride (NaBH₄) and stannous chloride (SnCl₂)) from the process enabled a simple and ultraclean procedure with an extremely low detection limit of 0.75 ng L⁻¹ for Hg²⁺ in urine samples. To the best of our knowledge, this is the first study to report the direct exploitation of a nano-TiO₂-coated microfluidic device for online sample preconcentration and on-site VG prior to ICP-MS measurement.[Full article]