It is highly desirable to measure fluid pressure and its pulsations through portable, handheld instruments and test kits, which allow a rapid, low-cost, and reliable quantification about liquid status, especially for cheaper, faster, and smarter point-of-care testing (POCT). Here, we proposed a portable self-powered smart fluid pressure sensor based on a liquid piston triboelectric nanogenerator (LP-TENG). By analyzing the characteristic signals due to the triboelectrification effect, electrostatic induction, and theory of the ideal gas equation, the developed sensor is able to determine the fluid’s pressure and flowing status quantitatively (e.g., moving direction, flow rate, blockages, pipe bursts, leakage, etc.). Here, a simply fabricated device has the highest accuracy of 0.4 kPa with a pressure range from 0 kPa to 30 kPa, which is superior to most commercial sensors. Furthermore, the electric performance can reach a resolution ratio of 10 mmHg, which is adequate to accurately identify the blood pressure (BP) level. Consequently, the self-powered LP-TENG is capable of real-time monitoring the fluid status, which can fit the need for diagnosing and detecting the BP level as a reliable POCT device in healthcare products, as well as other broad potential applications in manufacturing, transportation, and civil service.