Targeted liposomes are designed to target specific receptors overexpressed on the surfaces of cancer cells. This technique ensures site-specific drug delivery to reduce undesirable side effects while enhancing the efficiency of the encapsulated therapeutics. Upon reaching the tumor site, these liposomes can be triggered to release their content in a controlled manner using ultrasound (US). In this study, drug release from pegylated calcein-loaded liposomes modified with transferrin (Tf) and triggered with US was evaluated. Low-frequency ultrasound at 20-kHz using three different power densities (6.2 mW/cm2, 9 mW/cm2 and 10 mW/cm2) was found to increase calcein release. In addition, transferrin-conjugated pegylated liposomes (Tf-PEG liposomes) were found to be more sonosensitive compared to the non-targeted (control) liposomes. Calcein uptake by HeLa cells was found to be significantly higher with the Tf-PEG liposomes compared to the non-targeted control liposomes. This uptake was further enhanced following the exposure to low-frequency ultrasound (at 35 kHz). These findings show that targeted liposomes triggered with US have promising potential as a safe and effective drug delivery platform.