Here we present HPLC chip based chemical sensing. High Performance Liquid Chromatography (HPLC) is one of the most powerful, versatile, and widely used separation techniques. It allows separation, identification, purification, and/or quantification of the chemical compounds in complex mixtures. By miniaturizing HPLC system onto a chip, significantly lower sample and solvent requirements, higher mass sensitivity, and lower cost can be achieved. Moreover, portable HPLC chips can be used for field tests and/or networked sensing, which is impossible or impractical for conventional desktop HPLC systems. We have developed two integrated HPLC chips. One is demonstrated to perform on-chip sample injection, separation and detection of multiple anions in water (~25ppm). The other is capable of performing high-pressure separation of more complex samples, such as digested proteins. A palm-sized wireless LC system based on the liquid chromatography chips is also being developed.