Hard ticks are obligate blood-feeders belonging to the family Ixodidae. The saliva and salivary glands of ticks contain a wide variety of immuno-pharmacological active molecules that effectively modulate the activity of enzymes, antibodies, and amines involved in vasodilation, molecular adhesion, and cellular signaling. Ticks' saliva may contain proteins with antiangiogenic capabilities that inhibit the angiogenesis process and exclude wound healing, allowing ticks to feed on the blood of their hosts for an extended period of time. Antiangiogenic factors are being characterized for their ability to exert cytotoxic and cytolytic effects on tumor cells, making them promising candidates for anticancer therapy. The effects of salivary gland extracts (SGEs) from various Hyalomma species (i.e., Hyalomma anatolicum, H. marginatum, H. detritum, H. dromedarii, and H. schulzei) on tumor cells (HT-29) were investigated in this study. The SGEs from H. detritum had the strongest anti-survival effects on HT-29. The highest mean of HT-29 cell viability was obtained after exposure to H. schulzei SGEs. Hyalomma detritum SGEs had the lowest cytotoxicity to non-tumor cells (HFF) and H. schulzei SGEs had the highest cytotoxicity to HFF. The cytometric assessment revealed changes in HT-29 cells as well as a significantly higher frequency of apoptosis and necrosis after treatment with H. detritum SGEs than the other species. The results demonstrated that H. detritum SGEs have antiproliferative, anti-survival, and apoptotic potential. This finding suggests that the species is an appropriate candidate for further investigations to identify the molecules and mechanisms involved in the inhibitory effect of the SGEs.