To study the association between penetration enhancement effect of essential oils and drug properties of traditional Chinese medicines. Through literature research, 34 kinds of essential oils with the penetration enhancement effect were collected. The methods of frequency analysis and variable crosstab were used for intuitive analysis and association analysis. The association between penetration enhancement effect of essential oils and drug properties (four natures, five flavors, channel tropism) were analyzed by a general linear model. According to the findings, the essential oils with penetration enhancement effect were all sourced from acrid traditional Chinese medicines, because their positive drug nature contributed to the enhancement of the penetration effect of essential oil; five flavors had little effect on penetration enhancement (P = 0.6982), but four natures and channel tropism showed significant effects (P = 0.011, 0.077). In conclusion, there were obvious association and regularity between penetration enhancement effect of essential oils and drug properties of traditional Chinese medicine.