The self-enhanced electrochemiluminescence (ECL) with high sensitivity could be an effective method for anticancer drug screening with cell apoptosis monitoring. Here we reported an ultrasensitive ECL cytosensor for cell apoptosis monitoring by using self-enhanced electrochemiluminescent ruthenium-silica composite nanoparticles (Ru-N-SiNPs) labeled annexin V as signal probes. The Ru-N-SiNPs were first synthesized through simple hydrolysis of a novel precursor containing luminescent and intracoreactant groups in one molecule, which presented higher emission efficiency and enhanced ECL intensity due to the shorter electron-transfer path and less energy loss. Moreover, the as-proposed ECL cytosensor was successfully used to investigate efficiency of paclitaxel toward MDA-MB-231 breast cancer cell in the range from 1 nM to 200 nM with a detection limit of 0.3 nM and a correlation coefficient of 0.9917. The improved accuracy and excellent dynamic range revealed the potential applications in biomolecules diagnostics and cells detections, especially in living and complex systems.