Abstract: Proteins presence and differences of the expression level can clarify the physiological or pathological changes in organisms, so the quantitative detection of proteins is vital for disease mechanism research, diagnosis and prognosis evaluation. Traditional protein quantitation methods at the tissue level reflected the average protein expression in cells, but ignore the differences between individual cells. In contrast, approaches for quantitative detection at single-cell level can better reflect the differences. Recently, a number of approaches for such detection have been proposed, including microfluidics, microwell-based technology, optical fiber nanobiosensor, activity-based probe technology and mass spectrometry. The principles, advantages and drawbacks of these approaches are briefly introduced in this review.