In this work, the anti-tumor properties of the volatile oil from Zanthoxylum rhoifolium Lam leaves and some terpenes (alpha-humulene, beta-caryophyllene, alpha-pinene and beta-pinene) were investigated in vitro and in vivo using the Ehrlich ascites tumor model. Treatment of Ehrlich ascites tumor-bearing mice with 20 mg/kg of the volatile oil and beta-caryophyllene for 4 days has significantly increased survival, whereas administration of alpha-humulene, alpha-pinene and beta-pinene were ineffective in affording protection. Volatile oil and beta-caryophyllene exhibited little direct activity against Ehrlich tumor cells in vitro, while alpha-humulene, alpha-pinene and beta-pinene did not such activity. Investigation of the effects of the volatile oil (and terpenes) treatment on total natural killer cells (NK cell) activity from tumor-bearing mice as a possible mechanism of these compounds in vivo revealed that volatile oil and beta-caryophyllene significantly improved NK cell cytotoxicity against YAC-1, a Moloney virus-induced mouse T-cell lymphoma of A/SN origin and Ehrlich ascites cells. As expected, tumor growth in non-treated mice markedly suppressed NK cell cytolysis while the volatile oil and beta-caryophyllene reversed this effect when mice were treated with 20-mg/kg dosages of these compounds for 4 days. Summing up, volatile oil exhibits anti-tumor efficacy and significative immunomodulatory action in vivo, which may be related to beta-caryophyllene associated to the synergism of other natural compounds presented in volatile oil from Z. rhoifolium Lam leaves.